Studies on the effects of 5‐HT<sub>1A</sub> drugs in the pigeon

Barrett, James E.

doi:10.1002/ddr.430260309

Cited by 20 publications

(16 citation statements)

References 79 publications

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“…At the present time, studies conducted with the pigeon continue to suggest that punished responding in this species is reliably and markedly increased by a variety of drugs acting at the 5-HT1A receptor and these increases are comparable to those obtained with benzodiazepines (Brocco et al 1990;Nanry et al 1991;Barrett 1992;Pollard et al 1992). The reasons for the apparent species differences are not readily obvious but have been discussed in recent reviews (Barrett and Gleeson 1991;Barrett 1992).…”

Section: Conflict-type Proceduresmentioning

confidence: 67%

“…Flesinoxan appears to be the most potent of the 5-HT1A drugs in this procedure and tandospirone the least potent. The potency of these and other 5-HT1A drugs for increasing punished responding correlates quite highly (r--+ 0.83) with the ICs0 values of those drugs for their ability to displace [3H]8-OH-DPAT from pigeon brain homogenates (Barrett 1992), suggesting that increases in punished responding are mediated by this receptor subtype. Furthermore, the conflict procedure in the pigeon, at this point, appears to be among the most selective and sensitive of those procedures currently used to evaluate anxiolytic drugs (Barrett 1992).…”

Section: Conflict-type Proceduresmentioning

confidence: 94%

“…The potency of these and other 5-HT1A drugs for increasing punished responding correlates quite highly (r--+ 0.83) with the ICs0 values of those drugs for their ability to displace [3H]8-OH-DPAT from pigeon brain homogenates (Barrett 1992), suggesting that increases in punished responding are mediated by this receptor subtype. Furthermore, the conflict procedure in the pigeon, at this point, appears to be among the most selective and sensitive of those procedures currently used to evaluate anxiolytic drugs (Barrett 1992). For example, punished responding of the pigeon is also increased by a large number of known anxiolytic agents such as ethanol, the barbiturates and methaqualone, but increases in punished responding do not occur following administration of psychomotor stimulants, non-5-HTaA antidepressants, antipsychotic compounds or opioids.…”

Section: Conflict-type Proceduresmentioning

confidence: 94%

“…The reasons for the apparent species differences are not readily obvious but have been discussed in recent reviews (Barrett and Gleeson 1991;Barrett 1992). Fig.…”

Section: Conflict-type Proceduresmentioning

confidence: 96%

“…Partly in response to the need to find rodent test procedures that would predict clinical anxiolytic activity of buspirone and related drugs, a number of procedures no longer in use were re-examined or new procedures were introduced. Numerous review articles have appeared recently that summarize the use of animal models in the evaluation of anxiolytic drug activity, many with particular reference to 5-HT, including that of Handley and McBlane in the present volume (Briley et al 1991;De Vry et al 1991 ;Sanger 199i;Barrett 1992). 5-HT1A receptors are believed to play a role in a large number of behaviors which have been studied intensively (Lucki and Wieland 1990;Wilkinson and Dourish 1991;Lucki 1992).…”

mentioning

confidence: 97%

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5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions

Barrett¹,

Vanover²

1993

Psychopharmacology

151

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The introduction of buspirone for the treatment of anxiety, together with the eventual suggestion of a mode of action involving the serotonin (5-HT)1A receptor subtype, has generated considerable research activity and renewed interest in the potential role of 5-HT in anxiety. The further identification of multiple 5-HT1 receptors, coupled with the possibility that these subtypes potentially are involved in discrete biobehavioral regulation and pathophysiological conditions, has greatly expanded the search for tools capable of probing these receptors and has raised hopes for a new generation of more specific compounds to treat other disorders associated with the 5-HT system such as depression, aggression, and sleep and eating disturbances. The involvement of 5-HT in anxiety has prompted a careful reevaluation of several traditional areas of research. This has included those methods used in the in vivo evaluation of drugs in preclinical animal test procedures used to assess potential anxiolytic activity, as well as the mechanisms associated with adaptive changes occurring during long-term drug administration. The proliferation of various procedures for studying the anxiolytic effects of 5-HT drugs has not always been accompanied by systematic behavioral and pharmacological validation. At the present time, this area of research is characterized by numerous inconsistent findings. Procedures that are objective and impartial to the behavioral effects of drugs provide distinct advantages for addressing some of these issues, as will the results from carefully controlled clinical studies. The main objective of this article is to provide an overview of the recent developments in research involving the 5-HT system and anxiety. The emphasis will be on the 5-HT1 receptor system and a review of the results in the predominant animal models used to evaluate these drugs, as well as an overview of the mechanisms currently believed to be responsible for the therapeutic activity of this class of compounds. Studies with the pigeon are reviewed, since this species appears distinctly sensitive to the anxiolytic-like effects of 5-HT1A drugs in conflict procedures. Although chronic administration of 5-HT1A drugs appears necessary for clinical anxiolytic and antidepressant activity, the most noteworthy neuropharmacological effects in animals seem to occur in 5-HT2 and, perhaps, 5-HT3 receptors which are downregulated. Studies summarizing the activity of drugs interacting with 5-HT1C/2 and 5-HT3 receptor sites are also discussed as they too may be involved in anxiety or the actions of anxiolytic drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Conflict-type Proceduresmentioning

confidence: 67%

Section: Conflict-type Proceduresmentioning

confidence: 94%

Section: Conflict-type Proceduresmentioning

confidence: 94%

“…The reasons for the apparent species differences are not readily obvious but have been discussed in recent reviews (Barrett and Gleeson 1991;Barrett 1992). Fig.…”

Section: Conflict-type Proceduresmentioning

confidence: 96%

mentioning

confidence: 97%

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5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions

Barrett¹,

Vanover²

1993

Psychopharmacology

151

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Antianxiety Agents

Currie

2003

Burger's Medicinal Chemistry and Drug Discovery

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Anxiety is a complex and prevalent cluster of psychiatric disorders consisting of generalized anxiety disorder, panic disorder, social phobia, obsessive‐compulsive disorder, posttraumatic stress disorder, and specific phobias. These conditions are most commonly treated with benzodiazepines, buspirone, and serotonin reuptake inhibitors, all of which fall some way short of the ideal anxiolytic. The clinical applications, side effects, and drug metabolism of these medications are discussed. A multitude of neurotransmitter systems are implicated to a greater or lesser degree in the complex underlying neurobiology and physiology of anxiety, including GABA, serotonin, norepinephrine, glutamate, as well as neuropeptides such as CCK, CRF, and NPY. The increasing understanding of the roles of each neurobiological pathway provides a platform for medicinal chemistry efforts in anxiolytic research. The structure‐activity relationships of current medications and newer, investigational compounds interacting with these systems are discussed, as well as the future prospects for the development of improved anxiolytics.

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Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol

1994

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Buspirone is renowned for its highly inconsistent effects in animal models of anxiety. In the present study, the effects of acute (0.63-5.0 mg/kg) and chronic (1.25-5.0 mg/kg, daily, 15 days) buspirone treatment on the behaviour of mice in the elevated plus-maze test were assessed using a recently developed ethological scoring method. On acute administration, a selective reduction in risk assessment behaviours was observed at 1.25 mg/kg; these mild anxiolytic-like effects were maintained at higher doses (2.5-5.0 mg/kg) which also reduced measures of general activity. Similar, though more potent, effects were observed with chronic administration; the lowest dose tested (1.25 mg/kg) reduced open arm entries and total stretch attend postures while higher doses profoundly reduced all major indices of anxiety (traditional and novel) and, concomitantly, suppressed total entries and rearing. Acute administration of haloperidol (0.0125-0.1 mg/kg) appeared to mimic the behavioural suppressant effects of buspirone without selectively affecting anxiety-related measures at any dose. It is suggested that the anti-anxiety and behavioural suppressant profile of buspirone may reflect combined action at 5-HT1A and D2 receptors, respectively. Results are discussed in relation to the utility of risk assessment as a sensitive index of anxiety in models based upon unconditioned behaviour.

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

Cited by 20 publications

References 79 publications

5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions

5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions

Antianxiety Agents

Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol

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

Cited by 20 publications

References 79 publications

5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions

5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions

Antianxiety Agents

Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol

Contact Info

Product

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