Psychopharmacology (2004) 174:197–202 DOI 10.1007/s00213-003-1746-x ORIGINAL INVESTIGATION József Haller · Johanna Baranyi · Nikoletta Bakos · József Halµsz Social instability in female rats: effects on anxiety and buspirone efficacy Received: 20 June 2003 / Accepted: 22 November 2003 / Published online: 4 February 2004  Springer-Verlag 2004 Abstract Rationale: Buspirone produces inconsistent effects in laboratory rodents. Individual housing increases the efficacy of buspirone in male rats, suggesting that the effects of this (and other) compounds become conspicu- ous in animals showing anxiety-like states. The effect of individual housing was, however, weak, and evident only when the locomotor suppressive effects of buspirone dissipated (i.e. 4 h after treatment). Objectives: The effects of social instability, a recently developed model of social stress in female rats, was investigated on both anxiety and the anxiolytic efficacy of buspirone. Methods: Female rats were exposed to alternate days of isolation and moderate crowding for 2 weeks. Group composition was changed for each crowding phase. Basal anxiety and the anxiolytic efficacy of buspirone were assessed by the social interaction test of anxiety 24 h after the last crowding phase. Results: Crowding appeared stressful, as it increased plasma glucocorticoid levels in less than 1 h. Anxiety-like behaviours were increased by social instability compared with stable group housing. In group housed controls, buspirone markedly suppressed locomotion, without clear effects on anxiety-related behaviours. Social instability attenuated the locomotor suppressive effects of buspirone, but made the anxiolytic effects of the compound more conspicuous. The effects of individual housing (assessed earlier) and social instability (assessed here) on buspirone efficacy appear qualitatively different. Conclusions: Buspirone abolishes stress-in- duced anxiety, but has no anxiolytic effects in controls. This is consistent with clinical findings, as the drug decreases anxiety in anxious patients but not in healthy humans. Laboratory models involving stress-induced anxiety-like states can improve our understanding of drug effects and efficacy. Keywords Social instability · Stress · Anxiety · Anxiolytic · Buspirone · Female · Rats Introduction The clinical efficacy of buspirone is well documented (Strand et al. 1990; Steinberg 1994; Delle-Chiaie et al. 1995). In contrast to clinical findings, however, buspirone has been found ineffective or even anxiogenic in many animal studies (Johnston and File 1986; Bohus et al. 1990; Gao and Cutler 1993; Collinson and Dawson 1997; Rodgers 1997). In these latter studies, buspirone strongly suppressed locomotion, perhaps masking its anxiolytic effects. It has been postulated that inconsistencies are due to the current practice of generally testing the effects of anxiolytics in healthy animals (Haller 2001). Human data support this hypothesis as buspirone, rather than decreas- ing anxiety in healthy humans, induces sleepiness, drowsiness, dislike, feelings of tension, nervousness and even anxiety (Bond and Lader 1981; Murasaki et al. 1989; Rush et al. 1995). These effects are very similar to the pattern seen in the laboratory with healthy rodents. This raises the possibility that anxious animal and human subjects would also react to buspirone in similar ways. There are a few studies to support this assumption. For example, individual housing, which induces mild signs of anxiety in male rats, increased the efficacy of buspirone in the elevated plus-maze test (Haller et al. 2000; Majercsik et al. 2004). The effect was, however, only conspicuous after the suppressive effects of buspirone on locomotion dissipated, i.e. 4 h after treatment. Individual housing did not affect the suppressive effects of the compound on locomotion and, in addition, the effect of individual housing on buspirone efficacy (although significant) was relatively weak in both rats and mice. In these experi- ments, individual housing per se had a weak effect on anxiety. It was postulated that a stronger stressor, affect- ing anxiety more strongly, would further improve the efficacy of buspirone. J. Haller ( ) ) · J. Baranyi · N. Bakos · J. Halµsz Institute of Experimental Medicine, PO Box 67, 1450 Budapest, Hungary e-mail: haller@koki.hu Tel.: +36-12109406 Fax: +36-12109951