Behavioural despair in rats: a new model sensitive to antidepressant treatments.
TL;DR: Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.
About: This article is published in European Journal of Pharmacology.The article was published on 1978-02-15. It has received 3030 citations till now. The article focuses on the topics: Mianserin & Iprindole.
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TL;DR: This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST), and showed that SSRIs are not false negatives in the FST.
Abstract: This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST). A behavior sampling technique was developed to score the active behaviors swimming, climbing and diving, as well as immobility. The rat's behavior was recorded at the end of each 5-s period during the test session. The sampling technique was both reliable, as demonstrated by test-retest reliability and inter-rater reliability, and valid, as shown by comparison to the timing of behavior durations. Five different antidepressant drugs which block monoamine uptake and two 5-HT1A receptor agonists were shown to decrease immobility in the FST; however, they produced distinct patterns of active behaviors. The selective NE uptake inhibitors desipramine and maprotiline selectively increased climbing, whereas the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine selectively increased swimming. The 5-HT1A receptor agonists 8-OH-DPAT and gepirone also selectively increased swimming. These results show that:1) SSRIs are not false negatives in the FST; 2) at least two behaviorally distinct processes occur in the FST; and 3) enhancement of NE neurotransmission may mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may mediate swimming.
1,396 citations
Cites background from "Behavioural despair in rats: a new ..."
...The forced swimming test (FST) is a behavioral test which predicts the efficacy of antidepressant treatments ( Porsolt et al. 1977, 1978; Porsolt 1981)....
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TL;DR: The tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.
1,326 citations
TL;DR: The models with the highest overall validity are the intracranial self-stimulation, chronic stress and learned helplessness models in rats, and the primate separation model.
Abstract: Eighteen animal, models of depression are reviewed in relation to three sets of validating criteria. Of the 18 models, five could only be assessed for predictive, validity, seven could be assessed for predictive and face validity, and six could potentially have predictive, face and construct validity. Some traditional models (reserpine reversal, amphetamine potentiation) are rejected as invalid; the models with the highest overall validity are the intracranial self-stimulation, chronic stress and learned helplessness models in rats, and the primate separation model.
1,280 citations
TL;DR: The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent and may translate to some human conditions as suggested by the literature on eating disorders and obesity.
1,171 citations
Cites background from "Behavioural despair in rats: a new ..."
...Behavioral depression in animals can also be inferred using the forced-swim test, which measures swimming escape efforts vs. passive floating (Porsolt et al., 1978)....
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TL;DR: The diverse array of behavioral effects of serotonin form the basis for understanding its potential role as an etiological marker in psychiatric disorders and for the successful pharmacologic intervention of drugs regulating serotonin neurotransmission in behavior.
1,131 citations
References
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Book•
01 Jan 1975
TL;DR: In this article, the authors proposed a learned-helplessness model of depression and developed a set of guidelines for depression and learned helplessness, including depression, anxiety and unpredictability, childhood failure, sudden psychosomatic death controllability.
Abstract: Overview - depression, golden girl, anxiety and unpredictability, childhood failure, sudden psychosomatic death controllability - voluntary responding, response independence and response contingency - the superstition experiments experimental studies - helplessness saps the motivation to initiate responses - learned helplessness in the dog, the triadic design, motivational deficits in several species, generality of helplessness across situations helplessness disrupts to ability to learn helplessness produces emotional disturbance theory - cure and immunization - the statement of the theory, motivational disturbance, cognitive disturbance, emotional disturbance cure and prevention - limits on helplessness alternative theories - competing motor responses, adaptation, emotional exhaustion, and sensitization physiological approaches to helplessness depression - types of depression the learned-helplessness model of depression - ground rules, symptoms of depression and learned helplessness, etiology of depression and learned helplessness, a speculation about success and depression, cure of depression and learned helplessness, prevention of depression and learned helplessness anxiety and unpredictability - definition of unpredictability anxiety and the safety-signal hypothesis - the safety-signal hypothesis upredictability and monitoring fear stomach ulcers preference for predictability the relationship of predictability to controllability - self-administration, perceived control systematic desensitization and uncontrollability conclusion emotional development and education - the dance of development - reafference maternal deprivation predictability and controllability in childhood and adolescence - the classroom, poverty death - death from helplessness in animals death from helplessness in humans - institutionalized helplessness, death from helplessness in old age, infant death and anaclitic depression.
4,406 citations
TL;DR: Results presented below indicate that immobility is reduced by different treatments known to be therapeutic in depression including three drugs, iprindole, mianserin and viloxazine which although clinically active show little or no ‘antidepressant’ activity in the usual animal tests.
Abstract: A MAJOR problem in the search for new antidepressant drugs is the lack of animal models which both resemble depressive illness and are selectively sensitive to clinically effective antidepressant treatments. We have been working on a new behavioural model in the rat which attempts to meet these two requirements. The method is based on the observation that a rat, when forced to swim in a situation from which there is no escape, will, after an initial period of vigorous activity, eventually cease to move altogether making only those movements necessary to keep its head above water. We think that this characteristic and readily identifiable behavioural immobility indicates a state of despair in which the rat has learned that escape is impossible and resigns itself to the experimental conditions. This hypothesis receives support from results presented below which indicate that immobility is reduced by different treatments known to be therapeutic in depression including three drugs, iprindole, mianserin and viloxazine which although clinically active1–3 show little or no ‘antidepressant’ activity in the usual animal tests4–6.
4,172 citations
TL;DR: Though attachment theory incorporates much psychoanalytic thinking, many of its principles derive from ethology, cognitive psychology and control theory, and it conforms to the ordinary criteria of a scientific discipline.
Abstract: An account is given of attachment theory as a way of conceptualizing the propensity of human beings to make strong affectional bonds to particular others and of explaining the many forms of emotional distress and personality disturbance, including anxiety, anger, depression and emotional detachment, to which unwilling separation and loss give rise. Though it incorporates much psychoanalytic thinking, many of its principles derive from ethology, cognitive psychology and control theory. It conforms to the ordinary criteria of a scientific discipline. Certain common patterns of personality development, both healthy and pathological, are described in these terms, and also some of the common patterns of parenting that contribute to them.
1,945 citations
TL;DR: Dogs which had first learned to panel press in a harness in order to escape shock subsequently showed normal acquisition of escape/ avoidance behavior in a shuttle box, supporting a learned "helplessness" explanation of interference with escape responding.
Abstract: Dogs which had 1st learned to panel press in a harness in order to escape shock subsequently showed normal acquisition of escape/ avoidance behavior in a shuttle box. In contrast, yoked, inescapable shock in the harness produced profound interference with subsequent escape responding in the shuttle box. Initial experience with escape in the shuttle box led to enhanced panel pressing during inescapable shock in the harness and prevented interference with later responding in the shuttle box. Inescapable shock in the harness and failure to escape in the shuttle box produced interference with escape responding after a 7-day rest. These results were interpreted as supporting a learned "helplessness" explanation of interference with escape responding: Ss failed to escape shock in the shuttle box following inescapable shock in the harness because they had learned that shock termination was independent of responding. Overmier and Seligman (1967) have shown that the prior exposure of dogs to inescapable shock in a Pavlovian harness reliably results in interference with subsequent escape/avoidance
1,754 citations
Journal Article•
TL;DR: The tubular configuration of EXP-561 may be the most appropriate for blocking serotonin uptake and the conformation defined by the combination resulting from superimposition of the CP-24-441 and desipramine structures is apparently optimal for blocking norepinephrine uptake.
Abstract: Several compounds of relatively rigid molecular structure have been found to exert strong blockade of monoamine uptake by synaptosomal preparations of rat corpus striatum (dopamine and serotonin) and hypothalamus (norepinephrine). These include CP-24,441 (1R, 4S-N-methyl-4-phenyl-1,2,3,4-tetrahydro-1-naphthylamine), EXP-561 (4-phenylbicyclo[2.2.2]octan-1-amine), nomifensine and nefopam. The well-defined molecular geometry of the potent inhibitor EXP-561 is a fundamental structural/conformational requirement for uptake blocking activity for the large family of phenylbutylamine- and phenoxypropylamine-related inhibitors. The tubular configuration of EXP-561 may be the most appropriate for blocking serotonin uptake. The requisite conformation for blocking dopamine uptake appears to be defined by the combination resulting from superimposition of the CP-24,441 and nomifensine structures. The conformation defined by the combination resulting from superimposition of the CP-24-441 and desipramine structures is apparently optimal for blocking norepinephrine uptake. The conformational requirements for diphenylpropylamine-related uptake blockers may be defined by the rigid compound CP-39,332 (N-methyl-4-phenyl-1,2,3,4-tetrahydro-2-naphthylamine). The actual potency of any given inhibitor is probably modulated by additional structural and stereochemical factors.
505 citations