Showing papers on "Elevated plus maze published in 1991"

CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat

Abstract: The role of the neuropeptide corticotropin-releasing factor (CRF) in mediating the behavioral effects of ethanol withdrawal in the rat was examined using the elevated plus-maze test. In Experiment 1, CRF (0.5 µg ICV) reduced the percentage of time spent on the open arms of the elevated plus-maze, consistent with an “anxiogenic-like” effect. CRF also reduced the total number of arm entries, indicating a reduction in general activity. Low doses (5 and 25 µg ICV) of the CRF antagonist, alpha-helical CRF produced no behavioral effects in the elevated plus-maze, while a higher dose (50 µg ICV) elicited CRF-like activity. In experiment 2, rats were maintained for 2–3 weeks on a liquid diet containing ethanol (8.5–11.5% v/v) or sucrose. Eight hours after withdrawal from the ethanol diet rats displayed “anxiogenic-like” responses as well as a reduction in general activity in the elevated plus-maze compared with rats withdrawn from control diet. Alpha-helical CRF significantly antagonized the “anxiogenic-like” effects of ethanol withdrawal in the plus-maze. General activity and physical signs of ethanol withdrawal such as tail stiffness, body tremor and ventromedial distal flexion were unaffected by alpha-helical CRF. Blood Alcohol Levels (BALs) determined immediately after removal of the ethanol diet showed no group differences in ethanol consumption. These results suggest that increased activity of central CRF systems may mediate the anxiogenic effects of ethanol withdrawal.

Anxiolytic effect in the elevated plus-maze of the NMDA receptor antagonist AP7 microinjected into the dorsal periaqueductal grey

Abstract: In order to localise the often reported anxiolytic action of N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-7-phosphonoheptanoic acid (AP7) was injected into the dorsal periaqueductal grey (DPAG) of rats exposed to the elevated plus-maze model of anxiety. Doses of 0.2, 2 and 20 nmol AP7 caused a dose-dependent increase in the percentage of open arm entries, the effect of the last two doses being significantly different from control. A non-significant tendency to increase the percentage of time spent on the open arms of the maze was also noticed. In contrast, the total number of entries into either the open or enclosed arms was not affected. Injections of AP7 localized outside the DPAG were ineffective. Therefore, microinjection of AP7 into the DPAG caused a selective anxiolytic effect in the elevated plusmaze. It may be suggested that the DPAG is a site of the anxiolytic action of NMDA antagonists reported following systemic administration.

Ovarian endocrine status modulates the anxiolytic potency of diazepam and the efficacy of gamma-aminobutyric acid-benzodiazepine receptor-mediated chloride ion transport.

Abstract: The effect of ovarian steroid hormones on the behavioral and neurochemical sensitivity of the gamma-aminobutyric acid (GABA)-benzodiazepine (BZD) receptor chloride ion channel complex was studied. Locomotor activity and behavior in the elevated plus maze were examined in female rats of various ovarian states as was the efficacy and potency of GABA-stimulated chloride uptake in cortical synaptoneurosomes from proestrous and ovariectomized rats. A significant increase in the exploration of the open arms of the plus maze was observed in lactating females, in relation to diestrous, proestrous, ovariectomized, and pregnant females. The anxiolytic effect of diazepam (DZ) was decreased in ovariectomized females, in relation to proestrus females. Although 1.0 mg/kg DZ in proestrous females resulted in significant anxiolytic activity, this dose was ineffective in ovariectomized females but was reinstated by injection of estradiol benzoate and progesterone. A reduced efficacy of GABA-stimulated chloride ion transport in cortical synaptoneurosomes from ovariectomized females, in relation to that from proestrous females, was observed. Furthermore, the facilitative effect of DZ on the potency of GABA-stimulated chloride ion influx that was observed in cortical synaptoneurosomes from proestrous females was absent in synaptoneurosomes from ovariectomized females. These results are discussed in terms of the effect of ovarian steroids and reduced metabolites on GABA-BZD receptor-mediated functions.

GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures.

Abstract: Benzodiazepine (BZD) anxiolytics, through their activation of the BZD-GABA receptor complex, display robust anxiolytic-like effects following systemic administration in both conditioned and non-conditioned behavioral procedures. The present results show that the GABAA agonists muscimol (0.5-1.0 mg/kg), THIP (2.5-10.0 mg/kg), and isoguvacine (25.0 mg/kg) as well as the GABA transaminase (GABA-T) inhibitor AOAA (aminooxyacetic acid; 5.0-20.0 mg/kg) following intraperitoneal administration exert anxiolytic-like activity of similar magnitude to that of diazepam in two non-conditioned procedures, namely the social interaction and the elevated plus maze tests. We have also extended our original findings that the anti-epileptic drug sodium valproate exerts an anxiolytic-like effect in the Geller conflict paradigm, to show this agent's robust activity in the social interaction and elevated plus maze tests following systemic administration (100-400 mg/kg). These results show that GABAergic agents that facilitate GABA transmission are effective following systemic administration in non-conditioned anxiety procedures and may indicate potential therapeutic efficacy in certain anxiety states.

Early life protein malnutrition changes exploration of the elevated plus-maze and reactivity to anxiolytics.

Abstract: In order to investigate whether protein malnutrition in early life causes lasting changes in reactivity to anxiolytic drugs, exploration of the elevated plus-maze was used. Rat dams during lactation (21 days) and pups after weaning until day 49 of life were fed on 8% casein diet (M rats), while their well-nourished controls received 25% casein (W rats). From day 50 on all animals ate the same balanced diet. Experiments started on day 70. Under the non-drug condition, M rats tended to explore the open arms of the maze relatively more than W rats. Diazepam (0.5–5 mg/kg, IP) dose-dependently increased the percentage of open/total arm entries without significantly affecting the total number of arm entries in W rats. This selective anxiolytic effect of diazepam was considerably smaller in M rats. Ipsapirone (0.5–5 mg/kg) caused a similar though less pronounced anxiolytic effect in W rats, whereas the drug decreased both the % open/total and total arm entries in M rats. In contrast, ritanserin (0.05–1 mg/kg) significantly increased the % open/total arm entries in M rats only, though not in a dose-dependent way. Isamoltane (2.5–20 mg/kg) was ineffective on both M and W rats. These results indicate that early protein malnutrition causes long-lasting alterations in brain systems regulating emotional behaviour.

The effects of corticotrophin releasing factor (CRF) and handling stress on behavior in the elevated plus-maze test of anxiety:

Abstract: The effects on rodent anxiety of corticotrophin releasing factor (CRF), common experimental stressors and the CRF receptor blocker, α-helical CRF, were measured using the hole board and elevated plus-maze tests. Centrally administered (intracerebroventricular, i.c.v.) CRF increased anxiety in an anxioselective manner. α-Helical CRF (i.c.v) antagonized the effects of CRF, implicating central CRF receptors. Common experimental stressors, such as surgical implantation of cannulas and intraperitoneal injections of saline also selectively increased anxiety in the plus maze. Endogenous CRF binding to central CRF receptors probably mediates the anxiogenic effects of stressors, since α-helical CRF reversed the increased anxiety following surgery. Finally, repeated gentle handling seemed to blunt the anxiogenic effect of CRF. Handling also altered the effect of CRF on behavior, creating an apparently CRF-mediated suppression of rearing and exploration which was not present in rats not stressed with repeated handli...

Anxiogenic activity of isatin, a putative biological factor, in rodents.

Abstract: Isatin (2,3-dioxoindole) has been proposed as a new biological factor, responsible for at least part of the activity of tribulin, an endogenous monoamine oxidase and benzodiazepine receptor binding inhibitory factor, which may serve as an endocoid marker of stress and anxiety. The putative anxiogenic activity of isatin was investigated in rats and mice. The doses chosen for the study, namely 15 mg/kg i.p. in mice and 20 mg/kg i.p. in rats, were based on preliminary behavioural studies. Yohimbine, a well established anxiogenic agent, was used for comparison and used at doses of 2 and 2.5 mg/kg i.p. in mice and rats, respectively. The experimental paradigms chosen have been shown to stand the tests of validity and reliability. Isatin induced significant anxiogenic activity in the open-field and elevated plus-maze tests in mice, and the social interaction test in rats, which were comparable to those induced by yohimbine. In addition, both isatin and yohimbine attenuated the effects of the anxiolytic agent diazepam in the open-field test. The investigations indicate that isatin has significant anxiogenic effect and support the contention that it and/or its biotransformation products may be responsible for at least part of the activity of tribulin demonstrated previously in animal models and in clinical situations of stress and anxiety.

Effects of DN-2327, a new anxiolytic, diazepam and buspirone on exploratory activity of the rat in an elevated plus-maze.

Abstract: In the present study, the effects of a new anxiolytic, DN-2327, were compared to those of diazepam and buspirone in rats in the elevated plus-maze test. Two indices of anxiety were obtained in this test: the number of entries into the open arms expressed as a percentage of the total number of arm entries and the percentage of time spent on the open arms. Both a typical anxiolytic, diazepam, at 2.5, 5 and 10 mg/kg, PO and a new anxiolytic, DN-2327, at 2.5 and 5 mg/kg, PO dose-dependently increased the two indices: the percentage of time spent on the open arms and the percentage of open-arm entries. On the other hand, pentylenetetrazol (PTZ) at 10 and 20 mg/kg, IP decreased the two indices dose dependently as did yohimbine at 1.5 and 3 mg/kg, IP. DN-2327 at 2.5 and 5 mg/kg, PO and diazepam at 5 and 10 mg/kg, PO dose dependently and significantly increased the two indices that were suppressed following administration of PTZ at 10 mg/kg, IP. The effects of both DN-2327, 5 mg/kg, PO, and diazepam, 10 mg/kg, PO, on the two indices were significantly antagonized by the benzodiazepine (BZD) receptor antagonist flumazenil, 20 mg/kg, IP. Buspirone (2.5–20 mg/kg, PO) did not affect either of the two responses but dose dependently decreased the number of rearings, although in the Vogel conflict test, the anti-conflict activity of buspirone was equipotent to that of diazepam and DN-2327 at the minimum effective dose (10 mg/kg, PO) of each drug. In conclusion, the present experiment revealed that the anxiolytic effect of DN-2327 in this test was clear, whereas buspirone showed no apparent effect.

Anxiolytic activity of steroid anesthetic alphaxalone.

Abstract: The synthetic steroid anesthetic alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione) was studied in two behavioral paradigms known to be sensitive to anxiolytic drugs. In an elevated plus maze, alphaxalone produced an anxiolytic profile, significantly increasing the percentage of entries made into the open arms as well as the percentage of time spent on the open arms. In the conflict test, alphaxalone (6 and 8 mg/kg) produced a significant dose-dependent increase in punished responding and a decrease (8 mg/kg) in unpunished responding. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide (2-8 mg/kg). The increase in punished responding was not altered by the benzodiazepine antagonist Ro 15-1788 and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophospate (10 and 15 micrograms/kg). The gamma-aminobutyric acid agonists picrotoxin (1 mg/kg) and bicuculline (1 mg/kg) also failed to suppress the rate-increasing effects of alphaxalone in the conflict test. Chronic administration of alphaxalone for 1 week produced no tolerance to the anxiolytic behavioral effects. In addition, no changes in pain threshold were noted with alphaxalone (8 mg/kg) in the tail-flick analgesia test. These results suggest that the pharmacologic substrates for the anxiolytic actions of alphaxalone may be independent of either the benzodiazepine or picrotoxinin binding sites of the gamma-aminobutyric acid/benzodiazepine receptor complex.

Effects of HA-966 on conflict, social interaction, and plus maze behaviors

Abstract: Antagonists at the N-methyl-D-aspartate (NMDA) receptor share a number of properties, including anticonvulsant and anxiolytic-like behaviors. In the Cook and Davidson conditioned conflict paradigm, the NMDA receptor complex antagonists HA-966 (1 and 3 mg/kg), CPP (10 mg/kg), MK-801 (0.03 mg/kg), and the benzodiazepine, diazepam (3 and 10 mg/kg) significantly disinhibited conflict responding. Likewise, in the social interaction test and elevated plus maze assay, two non-conditioned paradigms predictive of anxiolytic activity, the NMDA antagonists HA-966, CPP, and MK-801, as well as diazepam, all significantly increased both social interaction time and open arm exploration time, respectively. In general, antagonism of the NMDA receptor complex results in anxiolytic behavior in rodents. Moreover, selective antagonism at the strychnine-insensitive glycine modulatory site (HA-966) may represent a new and novel class of compounds with potential therapeutic efficacy in anxiety.

Preclinical anxiolytic versus antipsychotic profiles of the 5‐HT3 antagonists ondansetron, zacopride, 3α‐tropanyl‐1H‐indole‐3‐carboxylic acid ester, and 1αH, 3α, 5αH‐tropan‐3‐yl‐3,5‐dichlorobenzoate

Abstract: In preclinical studies, the behavioral effects of serotonin antagonists at 5-HT3 receptor sites suggest potential efficacy in the treatment of anxiety and schizophrenia. The present study shows that 5-HT3 antagonists were effective in disinhibiting behavior in non-conditioned rodent models which elicit a behavioral state presumed to be analogous to anxiety, but were generally not effective in conditioned rodent anxiety models or in assays that are traditionally predictive of antipsychotic agents. Ondansetron (0.01–0.1 mg/kg), zacopride (0.1–1.0 mg/kg), ICS 205–930 (3α-tropanyl-1H-indole-3-carboxylic acid ester; 0.5 and 1.0 mg/kg), and MDL 72222 (1αH, 3α, 5αH-tropan-3-yl-3,5-dichlorobenzoate; 10.0 and 20.0 mg/kg) demonstrated anxiolytic effects in the social interaction and elevated plus maze procedures, while having little or no effect in a modified Cook and Davidson conflict procedure. Ondansetron, zacopride, and ICS 205–930 had no effect in neuroleptic screening procedures, such as the apomorphine climbing mouse assay (CMA), the pole climb avoidance (PCA) procedure, and the intracranial self-stimulation of the medial forebrain bundle (ICSS-MFB) assay. MDL 72222 had no effect on CMA but dose-dependently antagonized PCA (ED50 = 10.9 mg/kg) and ICSS-MFB (ED50 = 8.8 mg/kg). The results of the present study suggest that MDL 72222 possesses a profile of activity that is different from the other 5-HT3 antagonists tested and that, in general, 5-HT3 antagonists may prove to be efficacious in the treatment of certain forms of anxiety in man.

Evaluation of memory and anxiety in rats observed in the elevated plus-maze: effects of age and isolation.

Abstract: Twenty young (5 months) and 20 old (20-24 months) male Wistar rats, isolated or group housed, were tested in the elevated plus-maze to evaluate memory and anxiety. Memory was quantified by transfer latency (the time it took for the rat to move from the open arm to the enclosed arm) and anxiety by percent entries into the open arms. Isolation decreased the transfer latency of old (session 1 = 119.33 +/- 0.44 s; session 3 = 49.67 +/- 12.12 s) and young (session 1 = 111.20 +/- 8.80 s; session 3 = 55.90 +/- 13.60 s) rats, but did not modify percent entries into the open arms (old-isolated = 5.56 +/- 5.56; old-group housed = 10.18 +/- 7.05; young-isolated = 35.16 +/- 8.98; young-group housed = 33.21 +/- 8.11). Conversely, aging decreased percent entries into the open arms but did not affect the transfer latency of isolated or group-housed animals. The results indicate that the plus-maze test, unlike other methods for memory evaluation, does not discriminate between young and old rats. They also suggest that age increases anxiety and that isolation increases memory levels, but that there is no interaction between age and isolation with regard to their effect on memory and anxiety in rats.

Microinjection of propranolol into the dorsal periaqueductal gray causes an anxiolytic effect in the elevated plus-maze antagonized by ritanserin.

Abstract: The 5-HT1A/1B receptor antagonist propranolol was injected into the dorsal periaqueductal gray (DPAG) of rats exposed to the elevated plus-maze in order to investigate the participation in anxiety of 5-HT mechanisms operating in this brain region. Microinjection ofd,l- orl-propranolol into the DPAG increased the percentage of total arm entries without affecting the total number of entries into either open or enclosed arms of the maze, an effect characteristic of anxiolytic drugs injected systemically. The doses of 5 nmoll-propranolol and 10 nmold,l-propranolol caused anxiolytic effects of comparable magnitude, while the doses of 2.5 nmol of the former and 5 nmol of the latter were ineffective. Therefore, thel-isomer is likely to be the main one responsible for the pharmacological activity observed. In addition, the anxiolytic effect of 10 nmold,l-propranolol was antagonized by 10 nmol of the 5-HT2/1C receptor antagonist ritanserin, previously injected into the DPAG. The present as well as previously reported results suggest that the anxiolytic effect of propranolol injected into the DPAG is due to increased release of 5-HT acting on post-synaptic 5-HT2 receptors, resultant from blockade of 5-HT1B autoreceptors that inhibit amine release from serotonergic nerve endings.

Effects of 8-OH-DPAT and buspirone in a passive avoidance test and in the elevated plus-maze test in rats.

Abstract: Benzodiazepines are generally reported to be active in tests based on punished responding and in procedures involving exploratory behaviour, but the effects of 5-HT drugs thus far reported are inconsistent. The effects of the two 5-HT(1A) agonists 8-OH-DPAT and buspirone were studied in a passive avoidance test and in an elevated plus-maze test. In the passive avoidance test 8-OH-DPAT and buspirone, as well as diazepam and chlordiazepoxide, were effective, while, in the elevated plus-maze test, the two benzodiazepines were active whereas buspirone and 8-OH-DPAT were not. Comparing the effects of the 5-HT(1A) agonists with the two benzodiazepines in the passive avoidance test it is suggested that this test can be predictive for drugs influencing anxiety. The elevated plus-maze test has many advantages, such as the absence of noxious stimuli, compared to punishment procedures, but since the 5-HT(1A) agonists do not act as anxiolytic compounds in this test, it is suggested that the test does not provide a suitable model of anxiety.

Effects of mammillary body and mediodorsal thalamic lesions on elevated plus maze exploration.

Abstract: This study investigates the effects of lesioning the mamillary bodies (MB) or the dorsomedian nucleus (MD) of the thalamus on exploration of an elevated plus maze in mice. Exploration of 'open' and 'enclosed' arms of the maze has been used to evaluate anxiety in rodents. Normal rodents visit the enclosed arms more often than the open ones (innate agoraphobia). As operationally defined, the less the activity in the open arms, the more anxious is the subject. MB-lesioned mice entered the open alleys more often, and spent more time in them, than did controls, whereas the opposite was observed in MD-damaged subjects. It is suggested that, in mice given this task, MB lesions decrease anxiety and that MD lesions increase anxiety.

Effects of buspirone on antinociceptive and behaviourial responses to the elevated plus-maze in mice.

Abstract: Brief exposure to an elevated plus-maze (EPM) induces antinociception in male mice, a reaction that is not blocked by opiate receptor manipulations but which is completely inhibited by the benzodiazepine receptor agonist, diazepam. The present study examined the effects of a non-benzodiazepine anxiolytic, buspirone, on EPM antinociception and behaviour. EPM antinociception was completely abolished by 10mg/kg buspirone but was largely unaffected by lower doses (0.1-1.0mg/kg) of the compound. Behaviourally, 1-10mg/kg buspirone produced changes indicative of anxiety reduction, although the high dose anxiolytic profile was at least partially compromised by a general reduction in behaviour. Data are discussed in relation to the proposal that anxiety may be a critical factor in non-opioid forms of adaptive pain inhibition.

Mianserin in the treatment of ethanol withdrawal in the rat: prevention of behaviors indicative of anxiety.

Abstract: The present investigation was a pilot study to determine whether a single dose of mianserin, which produces long-term down-regulation of serotonin1C (5-HT1c) and 5-HT2 receptors, would prevent anxiogenic behaviors occurring during ethanol withdrawal as evaluated in the elevated plus maze. Male Long-Evans hooded rats were fed a liquid diet containing 4.5 percent ethanol for 4 days. Mianserin (20 mg/kg, i.p.) was injected on the morning of the third day of ethanol administration, or 48 hrs and 7 days prior to testing. When animals were tested either 12 hrs (acute withdrawal) or 5 days (protracted withdrawal) after the last dose of ethanol, anxiogenic behaviors were observed as a significant reduction in both percentage of open-arm entries and time spent on the open arms. In contrast, these anxiogenic behaviors were prevented by pre-injection with mianserin 48 hrs or 7 days prior to testing. Attenuation of this important symptom of ethanol withdrawal is of particular importance because, in addition to the nonaddicting properties of mianserin relative to current anxiolytics, the beneficial effects appear to be long lasting and can be achieved with a single dose.

Effect of a herbal psychotropic preparation, BR-16A (Mentat), on performance of mice on elevated plus-maze.

Abstract: Effect of BR-16A on various parameters of anxiety and transfer latency (TL) was studied in mice using elevated plus-maze. BR-16A (50-500 mg/kg) reduced the percentage of time spent in open arms and the percent preference of open arms for the first arm entry following acute as well as chronic drug administration. The total number of arm entries and the percentage of open arm entries remained unaffected. In combination with FG 7142 (10 mg/kg), BR-16A (100-500 mg/kg) further reduced the exploration of open arms. BR-16A reversed scopolamine (0.3 mg/kg)-induced delay in TL on 1st day. The reversal effect of BR-16A was enhanced by aniracetam (50 mg/kg). The data suggest anxiogenic and nootropic actions of BR-16A.

MK-801 produces antianxiety effect in elevated plus-maze in mice

Abstract: The antianxiety effect of the non-competitive NMDA receptor antagonist, MK-801, was investigated in the present study in the elevated plus-maze paradigm in mice. During a 5-min session of the test, the number of entries the animal made in open/and closed arm, preference of the animal for first entry, and average time each animal spent in open and closed arm were noted as parameters for anxiety-related movements. The effect of MK-801 was further explored by studying its interaction with the specific anxiolytic agent, diazepam; the anxiogenic beta carboline agent, FG 7142; and the central benzodiazepine receptor antagonist, flumazenil (RO 15–1788). MK-801 produced anxiolytic effects at all the doses investigated. It increased the preference of the animal for open arm in a dose-dependent manner and the effect was potentiated by diazepam. Both FG 7142 and flumazenil reversed the effects of MK-801 when these agents were concomitantly administered with MK-801. The study revealed the anxiolytic effect of MK-801, a non-competitive antagonist of NMDA-receptor, and also an interaction of the NMDA-receptor and GABA/BZ-receptor complex in anxiety-related behaviour in mice.

LY 171555-induced hyperdefensiveness in the mouse does not implicate benzodiazepine receptors.

Abstract: In naive mice the selective D2 agonist LY171555 dose-dependently (0.5-5 mg/kg) induces defensive responses toward non-aggressive conspecifics. In order to investigate possible anxiogenic properties of the D2 agonist, its behavioural effects were compared with those produced by the benzodiazepine receptor inverse agonist methyl-beta-carboline-3-carboxylate(beta-CCM) in the elevated plus maze and in social interactions with non-aggressive opponents. When tested in the elevated plus maze, mice injected with LY 171555 (0.005-1 mg/kg) showed no decrease either of the number of entries or of the time spent in the open arms. At 5 mg/kg an actual increase of these two measures was observed. By contrast, beta-CCM (1-3 mg/kg) dose-dependently decreased both the number of entries and the time spent in the open arms without altering locomotion. The effects of beta-CCM were antagonized by the benzodiazepine receptor antagonist RO 15-1788 (3 mg/kg) showing a selective involvement of benzodiazepine receptors in their modulation. On the other hand, beta-CCM, (1-3 mg/kg) did not produce significant effects on defensive behaviour of mice interacting with non-aggressive opponents and the defensive responses of mice treated with 1 mg/kg LY 171555 were not prevented by 5 mg/kg chlordiazepoxide. These results show that DA D2-mediated hyperdefensiveness and anxiety modulated by benzodiazepine receptors are unrelated phenomena and suggest that this behavioural response may represent a model of those forms of fear-related reaction that do not respond to benzodiazepine treatment.

Comparison of Acute and Chronic Treatment of Diazepam and Ritanserin in the Elevated Plus-maze Model of Anxiety

Abstract: Recently there has been increasing interest in drugs affecting brain serotonergic (5-HT) neurons as putative anxiolytic compounds. The most widely used anxiolytics, the benzodiazepines, are known to influence 5-HT neurotransmission but there is still controversy over whether this action is related to their anxiolytic effect (see Kahn et al., 1988; Thiebot, 1986). In the case of one class of 5-HT compounds, 5-HT2 receptor antagonists, ritanserin has been reported to be effective in the treatment of generalized anxiety disorder (Ceulemans et al., 1985). However, in animal behavioural models of anxiety the picture is somewhat confusing. For example, ritanserin shows no activity (neither anxiolytic or anxiogenic) in the reward/punishment conflict procedure (Ketelaars and Bruinvels, 1989), but these results need to be interpreted with caution as brain 5-HT neurons are also involved in the control of food and liquid intake, and ritanserin increases food intake in satiated rats (Fletcher, 1988).

Anxiogenic Effects of Scopolamine Observed in Rats in the Elevated Plus-maze

Abstract: In behavioural studies in animals, the centrally acting muscarinic anticholinergic agent, scopolamine, is classically used for its disrupting effects on learning and memory (Bartus et al., 1987). Scopolamine is also known to have significant effects on attention and distractability (Cheal, 1981). Thus, scopolamine induces a hyperreactivity to incidental disturbances such as occasional noises and movements of the observer, as well as causing frequent interruptions of ongoing activity and of continuity of exploration in an unfamiliar environment (Plotnik et al., 1975).

Effects of Repeated Administration of Diazepam to Rats on Locomotor Activity, Elevated Plus-maze and Various Brain Receptors

Abstract: The development of tolerance to and physical dependence upon benzodiazepines have been reported to occur with a number of compounds in man. Recently, various behavioural methods have been developed to measure these phenomena in animals. Tolerance to the anticonvulsant properties (Gonsalves and Gallager, 1986; Garratt et al., 1988; Haigh and Feely, 1988) and rota-rod ataxia (Miller et al., 1988) of benzodiazepines has been reported. Moreover, the elevated plus-maze test in mice or rats, which has been used to measure the level of anxious behaviour (Handley and Mithani, 1984; Pellow and File, 1985; Pellow et al., 1985), provides a useful model for measuring withdrawal effects of benzodiazepines. A number of reports have shown various contradictory neurochemical modifications at the benzodiazepine binding site (Distefano et al., 1979; Rosenberg and Chiu, 1981; Miller et al., 1988).