Involvement of 5-HT1A activity in the discriminative stimulus effects of imipramine

Barrett, James E.; Zhang, L.

doi:10.1016/0091-3057(91)90299-h

Cited by 16 publications

(2 citation statements)

References 13 publications

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“…Previous studies with rats in which attempts were made to train an antidepressant such as imipramine as a discriminative stimulus generally met with little success becuase the doses apparently were toxic over the time period required to establish the drug discrimination [Jones and Howard, 1987;Schechter, 1983;Shearman et al, 19781. Accordingly, the valuable neuropharmacological analyses of this important therapeutic drug class that are possible using Zhang and Barrett, 1991b;Barrett and Zhang, 1991a. the drug discrimination methods were impeded. Recently, however, it has been possible to establish a stable, reliable discrimination with the tricyclic antidepressant imipramine (3 .O or 5.6 mgikg), with no signs of toxicity over an extended period of testing (greater than 3 years).…”

Section: Antidepressant Drugs As Discriminative Stimulimentioning

confidence: 99%

Studies on the effects of 5‐HT_1A drugs in the pigeon

Barrett

1992

Drug Development Research

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A number of compounds with high receptor binding affinity for the 5-hydroxytryptamine (5-HT) receptor subtype designated as 5-HT,, can produce anxiolytic and/or antidepressant effects in humans. In contrast to the traditional benzodiazepine anxiolytics, many of the clinically efficacious 5-HTl, drugs are either ineffective or produce inconsistent results in traditional preclinical anxiolytic screens using behavioral procedures with rodents. In preclinical antidepressant models with these animals, however, effects of the 5-HT1, drugs, as well as those of traditional antidepressant compounds, are predictive of their antidepressant activity in humans. In contrast, 5-HTl, drugs are quite effective in pigeons studied under a rather conventional punishment or conflict-type procedure that is also sensitive to the benzodiazepine anxiolytics. However, traditional antidepressant compounds, such as the tricyclic drugs amitriptyline and irnipramine, as well as the 5-HT reuptake blockers such as fluoxetine, do not show effects similar to the newer 5-HTl, drugs in this procedure. Thus, in rodents, current antidepressant models are sensitive to drugs that appear to function through different mechanisms, whereas conflict-type procedures typically do not reveal anxiolytic-like effects with 5-HT,, drugs. The pigeon conflict procedure, however, discriminates between the 5-HTl A antidepressants and antidepressant drugs functioning through other systems, whereas the effects of known anxiolytics in this procedure are quite similar.Increases in punished responding with 5-HT1, drugs correlates highly (r= +0.83) with affinity for the 5-HTl, receptor in pigeons. This paper reviews behavioral studies conducted with the pigeon in which the focus has been on the analysis of 5-HTl , compounds and addresses additional work that is required to answer many of the outstanding questions about this new class of anxiolytic and/or antidepressant drugs. o

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Section: Antidepressant Drugs As Discriminative Stimulimentioning

confidence: 99%

Studies on the effects of 5‐HT_1A drugs in the pigeon

Barrett

1992

Drug Development Research

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“…Pigeons have been trained to discrimnate the antidepressant imipramine (3.0 and 5.6 mg/kg) from saline (Zhang & Barrett, 1991), and this stimulus generalized to a number of other antidepressant drugs such as desipramine, amitriptyline, doxepin, nomifensine, and tomoxetine but not to the 5-HT uptake inhibitor fluoxetine. In a follow-up study, the imipramine stimulus generalized to the 5-HT 1A receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and gepirone but not to the 5-HT 2 receptor antagonist ritanserin (Barrett & Zhang, 1991).…”

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Discriminative stimulus properties of the serotonin uptake inhibitor sertraline.

Kreiss¹,

Lucki²

1994

Experimental and Clinical Psychopharmacology

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Rats (Rattus norvegicus) were trained to discriminate the stimulus properties of the antidepressant serotonin (5-hydroxytryptamine; 5-HT) uptake inhibitor sertraline (10 mg/kg) from saline using the discriminated taste aversion procedure. Three other selective 5-HT uptake inhibitors, fluvoxamine (5.6 and 10.0 mg/kg), fluoxetine (10.0 mg/kg), and paroxetine (10.0 mg/kg), substituted completely for the stimulus properties of sertraline. Selective inhibitors of norepinephrine uptake, desipramine and maprotiline, also substituted for the sertraline stimulus at 18.0 mg/kg. The results of the present study show that rats can be trained to respond to sertraline as a discriminative stimulus and that sertraline generalizes to other 5-HT uptake inhibitors that are members of a class of antidepressant drugs.Clinically effective antidepressant drugs represent a pharmacologically diverse group of compounds. Antidepressant drugs include monoamine oxidase inhibitors, selective and nonselective inhibitors of norepinephrine (NE) and serotonin (5hydroxytryptamine; 5-HT) uptake, and atypical compounds (for review, see Frazer & Brunswick, 1990;Heninger & Charney, 1987). The physiological mechanisms mediating the clinical efficacy of these compounds are unknown. The technique of drug discrimination provides a method by which the effects of antidepressant drugs can be measured in a behaviorally functional context and might provide information concerning the neural substrates associated with the behavioral effects of these compounds. Drug-discrimination procedures involve training an animal to respond differentially on administration of two selected compounds that produce different internal states, usually a drug and saline.

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The Discriminative Stimulus Properties of Drugs Used to Treat Depression and Anxiety

Prus

Porter

2016

The Behavioral Neuroscience of Drug Discrimination

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Drug discrimination is a powerful tool for evaluating the stimulus effects of psychoactive drugs and for linking these effects to pharmacological mechanisms. This chapter reviews the primary findings from drug discrimination studies of antidepressant and anxiolytic drugs, including novel pharmacological mechanisms. The stimulus properties revealed from these animal studies largely correspond to the receptor affinities of antidepressant and anxiolytic drugs, indicating that subjective effects may correspond to either therapeutic or side effects of these medications. We discuss drug discrimination findings concerning adjunctive medications and novel pharmacologic strategies in antidepressant and anxiolytic research. Future directions for drug discrimination work include an urgent need to explore the subjective effects of medications in animal models, to better understand shifts in stimulus sensitivity during prolonged treatments, and to further characterize stimulus effects in female subjects. We conclude that drug discrimination is an informative preclinical procedure that reveals the interoceptive effects of pharmacological mechanisms as they relate to behaviors that are not captured in other preclinical models.

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Involvement of 5-HT1A activity in the discriminative stimulus effects of imipramine

Cited by 16 publications

References 13 publications

Studies on the effects of 5‐HT_1A drugs in the pigeon

Studies on the effects of 5‐HT_1A drugs in the pigeon

Discriminative stimulus properties of the serotonin uptake inhibitor sertraline.

The Discriminative Stimulus Properties of Drugs Used to Treat Depression and Anxiety

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Involvement of 5-HT1A activity in the discriminative stimulus effects of imipramine

Cited by 16 publications

References 13 publications

Studies on the effects of 5‐HT1A drugs in the pigeon

Studies on the effects of 5‐HT1A drugs in the pigeon

Discriminative stimulus properties of the serotonin uptake inhibitor sertraline.

The Discriminative Stimulus Properties of Drugs Used to Treat Depression and Anxiety

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Product

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Studies on the effects of 5‐HT_1A drugs in the pigeon

Studies on the effects of 5‐HT_1A drugs in the pigeon