Showing papers on "Arecoline published in 1987"

Development of amygdaloid cholinergic mediation of passive avoidance learning in the rat. I. Muscarinic mechanisms.

Abstract: Passive avoidance learning was studied in young rats 13–30 days of age following bilateral injections of saline or antimuscarinic and/or muscarinic agents into three amygdaloid nuclei — lateral (L), basolateral (BL), and cortical (CO). While acquisition was not influenced by saline injections into various other cerebral structures, it was significantly altered by similar injections into these amygdaloid nuclei, especially by those into the BL nucleus, suggesting that this nucleus is particularly involved in passive avoidance learning. Atropine induced significant deficits from as early as 13 days on. These deficits increased and were of similar strength after injections into any of the three studied nuclei until day 16; after that age, they diminished slightly following CO and L nuclei administration, while remaining substantial after BL nucleus injections at all ages, even at 30 days. No facilitatory effects could be elicited by arecoline injected alone, while arecoline could antagonize the disturbing effect of atropine, when given in combination, from day 13 on. These results suggest a muscarinic cholinergic mediation of passive avoidance learning through the synaptic elements located in the basal lateral part of the amygdala in the young rat.

Effects of arecoline and pilocarpine on learning ability in marmosets pretreated with hemicholinium-3.

Abstract: Common marmosets (Callithrix jacchus) were trained to perform serial reversal position discrimination tasks in a Wisconsin General Test Apparatus. Intraventricular injection of hemicholinium-3 4 h before testing resulted in a profound impairment of position discrimination learning which could be overcome by the intramuscular administration of low doses of the muscarinic agonists, arecoline or pilocarpine.

Discriminative stimulus properties of muscarinic agonists.

Abstract: In a two-lever, food-reinforced drug-discrimination paradigm separate groups of rats were trained to discriminate either arecoline, pilocarpine or oxotremorine from saline. The discriminative cues of all three agonists were potently blocked by scopolamine, but only by 30–60 fold higher doses of methylscopolamine. The three agonists all suppressed overall response rate. These rate-suppressant effects were not blocked by scopolamine in doses which blocked the discriminative cues. In generalization tests, arecoline elicited selection of the drug-appropriate lever in all groups of trained animals. Pilocarpine was discriminated as drug by all pilocarpine-trained animals and by a majority of oxotremorine-trained animals, but was not significantly discriminated by the arecoline-trained group. Oxotremorine was discriminated by all oxotremorine-trained animals but only by some pilocarpine-trained animals, and was not significantly discriminated by the arecoline-trained group. Morphine, haloperidol, chlordiazepoxide, pentobarbital and nicotine were not generalized to any of the training drugs. The discriminative stimuli produced by the training drugs are therefore specific and exhibit properties indicative of an origin at central muscarinic receptors but may not be identical.

Motor responses of autoimmune NZB/B1NJ and C57BL/6Nnia mice to arecoline and nicotine.

Abstract: In 11-13 month C57BL/6Nnia mice, arecoline produced a dose-dependent decrease in motor activity at doses of 0.64-2.5 mg/kg, whereas at doses of 5.0-20.0 mg/kg arecoline produced a dose-dependent increase in motor activity. In marked contrast, age-matched NZB/B1NJ (New Zealand Black) mice failed to exhibit the first phase of the response, but showed a greater dose-dependent increase in motor activity following the doses of 10 and 20 mg/kg. Nicotine, 0.64-2.5 mg/kg, produced a dose-dependent decrease in motor activity in both strains. The effects of arecoline and nicotine were antagonized by scopolamine (2.5 mg/kg) and mecamylamine (1.0 mg/kg), respectively. These findings suggest that muscarinic neurotransmission may be altered in NZB/B1NJ mice, which produce brain-reactive autoantibodies, exhibit learning/memory dysfunctions, and also exhibit a loss of neurons staining positive for choline acetyltransferase.

Protection against hypoxia-induced lethality in mice: a comparison of the effects of hypothermia and drugs.

Abstract: The role of hypothermia in the antihypoxic effects of drugs was examined in the present experiments. The effects of environmentally induced hypothermia and drugs were tested by exposing mice to 100% nitrogen gas for 80 sec and counting the number of survivors. In a series of 68 vehicle control groups, the mean of mice surviving the test was 8.6% (SEM = 1.4). Hypothermia induced by lowering the ambient temperature or by isolating mice for a brief period increased the number surviving hypoxia, and the per cent of animals surviving was linearly related to body temperature. When the effects of drugs were compared to that of hypothermia, several drugs were found which protected mice from hypoxia to a greater extent than hypothermia alone. Active substances included the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and diazepam, but not primidone. Physostigmine and the muscarinic agonist oxotremorine also caused significant protection, while the effects of nicotine could be completely accounted for by hypothermia. Arecoline had a biphasic, time-dependent effect that may be explained by a combination of muscarinic and nicotinic actions. The effects of the muscarinic agonists are centrally mediated, since they could be blocked by low doses of scopolamine HCl, but not by the quaternary analog scopolamine methyl nitrate. Furthermore, the antihypoxic effect of physostigmine was not mimicked by the peripherally acting acetylcholinesterase inhibitor, neostigmine. These results suggest that some drugs do have protective effects against hypoxia which are independent of drug-induced hypothermia and that these effects may be mediated through the CNS.

Muscarinic and Nicotinic Mechanisms of Seizures Induced by Cholinesterase Inhibitors: Observations on Diazepam and Midazolam as Antagonists

Abstract: The gross behavioral and EEG seizure-inducing effects of various cholinesterase inhibitors (ChEI) were compared to the cholinergic agonists arecoline and nicotine, and the classic convulsants pentylenetetrazol and strychnine in unanesthetized rats. It was also our purpose to determine the possible anticonvulsant activity of potential antagonists. Femoral arterial and venous cannulae, EEG (epidural) and EKG (Lead II) electrodes were surgically implanted under halothane-oxygen anesthesia into adult Sprague-Dawley male rats (200–350 gm). Upon recovery from halothane anesthesia each rat received one of the following: 1) a directly acting cholinergic agonist (arecoline or nicotine); 2) a cholinesterase inhibitor, diethyi-p-nitrophenylphosphate (paraoxon), diisopropylfluorophosphate (DFP), neostigmine, or physostigmine; or 3) a central nervous system convulsant (pentylenetetrazol or strychnine).