5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: More than 30 years of research

https://doi.org/10.1016/0163-7258(95)98597-JGet rights and content

Abstract

An overview of the behavioral data arising from the vast literature concerning the involvement of 5-hydroxytryptamine (5-HT) neurotransmission in the regulation of anxiety is presented. More than 1300 experiments were carried out in this area and they provide evidence that: (1) results obtained in ethologically based animal models of anxiety with drugs stimulating 5-HT transmission are most consistent with the classic 5-HT hypothesis of anxiety in that they show an increase in animals' emotional reactivity; (2) no category of anti-anxiety models are selectively sensitive to the anxiolytic-like effects of drugs targetting 5-HT1A, 5-HT2A or 5-HT2C receptor subtypes; (3) anxiolytic-like effects of 5-HT3 receptor antagonists, in the great part, are revealed by models based on spontaneous behaviors. Taken together, these observations lead to the conclusion that different 5-HT mechanisms, mediated by different receptor subtypes, are involved in the genesis of anxiety.

References (512)

  • F Borsini et al.

    The effects of DAU 6215, a novel 5HT-3 antagonist, in animal models of anxiety

    Pharmacol. Res.

    (1993)
  • A.T Bruinvels et al.

    Homogeneous 5-HT1D recognition sites in the human subtantia nigra identified with a new iodinated radioligand

    Eur. J. Pharmac.

    (1991)
  • M Carli et al.

    Effect of 5-HT1A agonists on stress-induced deficit in open field locomotor activity of rats: evidence that this model identifies anxiolytic-like activity

    Neuropharmacology

    (1989)
  • M Carli et al.

    Stimulation of hippocampal 5-HT1A-receptors causes amnesia and anxiolytic-like but not antidepressant-like effects in the rat

    Eur. J. Pharmac.

    (1993)
  • P.L Carlton et al.

    Attenuated habituation due to parachlorophenylalanine

    Pharmac. Biochem. Behav.

    (1973)
  • P Chopin et al.

    Animal models of anxiety: the effect of compounds that modify serotonergic function

    TIPS

    (1987)
  • A Clarke et al.

    Effects of ACTH, benzodiazepines and 5-HT antagonists on escape from periaqueductal grey stimulation in the rat

    Prog. Neuro-Psychopharmac. biol. Psychiat.

    (1982)
  • R.L Conner et al.

    Parachlorophenylalanine and habituation to repetitive auditory startle stimuli in rats

    Physiol. Behav.

    (1970)
  • B Costall et al.

    Exploration of mice in a black and white test box: validation as a model of anxiety

    Pharmac. Biochem. Behav.

    (1989)
  • B Costall et al.

    The effect of the 5-HT3 receptor antagonist, RS-42358-197, in animal models of anxiety

    Eur. J. Pharmac.

    (1993)
  • D.B Adams

    Brain mechanisms for offense, defense and submission

    Behav. Brain Sci.

    (1979)
  • G.K Aghajanian et al.

    Localization of tritiated serotonin in rat brain by electron-microscopic autoradiography

    J. Pharmac. exp. Ther.

    (1967)
  • S.T Ahlers et al.

    Antagonism studies with BMY-7378 and NAN-190: effects on 8-hydroxy-2-(di-n-propylamino)tetralin-induced increases in punished responding of pigeons

    J. Pharmac. exp. Ther.

    (1992)
  • T Akai et al.

    Anxiolytic effects of lisuride and its action to central 5-HT1A receptors

    Folia pharmac. jap.

    (1991)
  • L.E Allen et al.

    Pharmacologic effects of MJ 9022-1, a potential tranquilizing agent

    Arzneimittel-Forsch.

    (1974)
  • S.S Almeida et al.

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

    Psychopharmacology

    (1991)
  • M Amano et al.

    Comparison of the anticonflict effect of buspirone and its major metabolite 1-(2-pyrimidyl)-piperazine (1-PP) in rats

    Jap. J. Pharmac.

    (1993)
  • C.L Amrick et al.

    A comparison of the anticonflict activity of serotonin agonists and antagonists in rats

    Soc. Neurosci. Abstr.

    (1986)
  • G Andersson et al.

    Neuropharmacology of FG5893. a new psychotropic drug with high affinity for both the 5-HT1A and the 5-HT2 serotonin receptor

  • T.H Andree et al.

    Preclinical neuropharmacological profile of WY-48,723, a potent serotonin (5-HT1A) agonist

    Soc. Neurosci. Abstr.

    (1988)
  • N Andrews et al.

    Increased 5-HT release mediates the anxiogenic response during benzodiazepine withdrawal: a review of supporting neurochemical and behavioural evidence

    Psychopharmacology

    (1993)
  • M.H Aprison et al.

    Neurochemical correlates of behavior — II. Correlation of brain monoamine oxidase activity with behavioural changes after iproniazid and 5-hydroxytryptophan administration

    J. Neurochem.

    (1961)
  • F Arriaga et al.

    Ritanserin an original sleep quality improving agent in generalized anxiety disorders

  • E.A Audi et al.

    Mediation by serotonin of the antiaversive effect of zimelidine and propranolol injected into the dorsal midbrain central grey

    J. Psychopharmac.

    (1988)
  • E.A Audi et al.

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

    Psychopharmacology

    (1991)
  • V Audinot et al.

    Receptorial profiles of atypical antipsychotics at cloned human dopamine D2 and D3 receptors and at rat D2 and 5-HTIC2 receptors in vitro/ex vivo

    Soc. Neurosci. Abstr.

    (1993)
  • A Baduel et al.

    Comparison of the effects of buspirone, diazepam, haloperidol and sulpiride on a conflict schedule in rats

    Neurosci. Lett.

    (1986)
  • N.M Barnes et al.

    Identification of 5-HT3 recognition sites in human brain tissue using [3H]zacopride

    J. Pharm. Pharmac.

    (1988)
  • J.E Barrett

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

    Drug Dev. Res.

    (1992)
  • J.E Barrett et al.

    Anxiolytic effects of 5-HT1A agonists, 5-HT3 antagonists and benzodiazepines: conflict and drug discrimination studies

  • J.E Barrett et al.

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

    Psychopharmacology

    (1993)
  • J.E Barrett et al.

    Anticonflict and discriminative stimulus effects of the 5-HT1A compounds WY-47,846 and WY-48,723 and the mixed 5-HT1A agonist/5-HT2 antagonist WY-50,324 in pigeons

    Drug Dev. Res.

    (1991)
  • J.E Barrett et al.

    Behavioral and pharmacological analysis of the effects of buspirone

    FASEB J.

    (1984)
  • J.E Barrett et al.

    Behavioral studies with anxiolytic drugs. III. Antipunishment actions of buspirone in the pigeon do not involve benzodiazepine receptor mechanisms

    J. Pharmac. exp. Ther.

    (1986)
  • J.E Barrett et al.

    Anticonflict effects of the 5-HT1A compound flesinoxan

    J. Psychopharmac.

    (1989)
  • S.R.G Beckett et al.

    Attenuation of chemically induced defense response of 5-HT1 receptor agonists administered into the periaqueductal gray

    Psychopharmacology

    (1992)
  • B Beer et al.

    Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety

    Science

    (1972)
  • D Benjamin et al.

    Mianserin-induced 5-HT2 receptor downregulation results in anxiolytic effects in the elevated plus-maze test

    Drug Dev. Res.

    (1992)
  • D Benton et al.

    The influence of psychotropic drugs on the ultrasonic calling of mouse pups

    Psychopharmacology

    (1988)
  • H.H.G Berendsen et al.

    Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice

    Br. J. Pharmac.

    (1990)
  • Cited by (0)

    Present address—Synthélabo Recherche (L.E.R.S.), CNS Pharmacology Group, 31, avenue Paul Vaillant-Couturier, B.P. 110, 92225 Bagneux Cedex, France.

    View full text