Antiaggresive and Anxiolytic Effects of Gepirone in Mice, and Their Attenuation by WAY 100635

Mendoza, Diana L.

doi:10.1016/s0091-3057(98)00171-3

Cited by 31 publications

(14 citation statements)

References 42 publications

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“…These doses of WAY 100635 had no significant effect on plus-maze anxiety-like behavior in +/+ controls either in this experiment or in our pilot studies. At the doses presently tested, systemic administration of WAY 100635 and other selective antagonists, such as mPPI, has been found to exert anxiolytic-like effects in the various rodent tasks, including the elevated plus maze, in some studies (eg Cao and Rodgers, 1997a, b;Griebel et al, 1999Griebel et al, , 2000, but not others (eg File et al, 1996;Collinson and Dawson, 1997;Mendoza et al, 1999;Hata et al, 2001; for reviews see Griebel, 1995;Cao and Rodgers, 1997a, b;Griebel et al, 1999). One possible reason for this variability is that the effects of 5-HT 1A receptor antagonists will depend upon basal serotonergic tone and baseline anxietylike behavior evoked in a given test situation, which will vary somewhat across laboratories (Rodgers and Cao, 1999).…”

Section: Discussionmentioning

confidence: 96%

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Holmes

Yang

Lesch

et al. 2003

Neuropsychopharmacol

285

203

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The serotonin transporter (5-HTT) regulates serotonergic neurotransmission via clearance of extracellular serotonin. Abnormalities in 5-HTT expression or function are found in mood and anxiety disorders, and the 5-HTT is a major target for antidepressants and anxiolytics. The 5-HTT is further implicated in the pathophysiology of these disorders by evidence that genetic variation in the promoter region of the HTT (SLC6A4) is associated with individual differences in anxiety and neural responses to fear. To further evaluate the role of the 5-HTT in anxiety, we employed a mouse model in which the 5-HTT gene (htt) was constitutively inactivated. 5-HTT À/À mice were characterized for anxiety-related behaviors using a battery of tests (elevated plus maze, light2dark exploration test, emergence test, and open field test). Male and female 5-HTT À/À mice showed robust phenotypic abnormalities as compared to +/+ littermates, suggestive of increased anxiety-like behavior and inhibited exploratory locomotion. The selective 5-HT 1A receptor antagonist, WAY 100635 (0.05-0.3 mg/kg), produced a significant anxiolytic-like effect in the elevated plus maze in 5-HTT À/À mice, but not +/+ controls. The present findings demonstrate abnormal behavioral phenotypes in 5-HTT null mutant mice in tests for anxiety-like and exploratory behavior, and suggest a role for the 5-HT 1A receptor in mediating these abnormalities. 5-HTT null mutant mice provide a model to investigate the role of the 5-HTT in mood and anxiety disorders.

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Section: Discussionmentioning

confidence: 96%

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Holmes

Yang

Lesch

et al. 2003

Neuropsychopharmacol

285

203

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“…The reversal of these effects by antagonists such as WAY 100,635 points to the 5-HT 1A receptor as the critical site of action (Miczek et al 1998b;Mendoza et al 1999;de Boer et al 2000), although the contribution of 5-HT 1D receptors needs to be explored. However, there is conflicting evidence on whether 5-HT 1A receptor agonists exert their anti-aggressive effects primarily through pre-or post-synaptic receptors.…”

Section: -Ht 1 Receptor Familymentioning

confidence: 99%

Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and ?-aminobutyric acid systems

et al. 2002

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(1) The preclinical focus on the behavioral characteristics and determinants of intense aggression promises to be most relevant to the clinical distinction between the proposed impulsive-reactive-hostile-affective subtypes of human aggression and the controlled-proactive-instrumental-predatory subtypes of aggression. The neural circuits for many types of human and animal aggression critically involve serotonin, dopamine and gamma-aminobutyric acid (GABA) and specific receptor subtypes. (2) The dynamic changes in frontal cortical serotonin that are triggered by engaging in aggressive behavior imply that serotonergic drug effects are largely determined by the functional state of the receptors at the time of drug treatment. Of the numerous 5-HT receptors currently identified, the 5-HT(1B) receptors offer a promising target for reducing impulsive aggressive behavior, particularly if the action can be limited to sites in the central nervous system. (3) Aggressive confrontations are salient stressors, both for the aggressor as well as the victim of aggression, that are accompanied by activation of the mesocorticolimbic but not the striatal dopamine system. Dopaminergic manipulations, particularly targeting the D(2) receptor family, can influence aggressive behavior in animals and human patients, suggesting that mesocorticolimbic dopamine may have important enabling or permissive functions. (4) GABA is critical in the neurochemical control of aggressive behavior as evidenced by studies that directly modify GABAergic neurotransmission and neurochemical studies that correlate GABA measurements with aggressive behavioral responses in several animal species. The GABA(A) receptor complex is a mechanism through which certain benzodiazepines and alcohol enhance and inhibit aggressive behaviors. Social and pharmacological experiences decisively determine the effects of GABAergic positive modulators on aggression.

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“…The 5-HT 1A partial agonist gepirone has shown mixed results, although negative findings have also been reported for buspirone [Pellow and File, 1986]. Some studies have reported anxiolytic effects [Mendoza et al, 1999;Stefánski et al, 1992], whereas others have reported either no effect or anxiogenic effects of acute doses of gepirone, although chronic administration of gepirone was reported to be anxiolytic [Maisonnette et al, 1993;Silva and Brandao, 2000]. In contrast, 5-HT 1B agonists (e.g., mCPP, CGS12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a] quinoxaline), TFMPP (1-[3-fluoromethyl)phenyl]-piperazine)) have been found to produce anxiety-like behaviors in various animal models of anxiety [Benjamin et al, 1990;Winslow and Insel, 1991].…”

Section: Monoaminergic Sites Serotonergic Receptorsmentioning

confidence: 99%

Animal models of the anxiogenic effects of ethanol withdrawal

Gatch¹,

Lal²

2001

Drug Development Research

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Although anxiety is a major feature of ethanol withdrawal (EW) and much of treatment related to EW is focused on amelioration of the anxiety experienced during EW, less attention has been given to the anxiogenic effects of EW than to the convulsant effects. In this article, we review the animal literature on the anxiogenic effects of EW. Both GABA A and serotonin (5-HT) receptors are important targets in the treatment of anxiety. The roles of each of these two receptors on the anxiogenic effects of EW as well as their potential interrelation are discussed. The contribution of other receptor systems to the modulation of these effects is reviewed. Additionally, males and females show very different levels of anxiety during EW and studies on the role of the HPA axis in mediating these effects are examined. Finally, potential directions for better treatments for EW are discussed. Drug Dev. Res. 54:95-115, 2001.

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Antiaggresive and Anxiolytic Effects of Gepirone in Mice, and Their Attenuation by WAY 100635

Cited by 31 publications

References 42 publications

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Mice Lacking the Serotonin Transporter Exhibit 5-HT1A Receptor-Mediated Abnormalities in Tests for Anxiety-like Behavior

Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and ?-aminobutyric acid systems

Animal models of the anxiogenic effects of ethanol withdrawal

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