Ž . European Journal of Pharmacology 399 2000 43–47 www.elsevier.nlrlocaterejphar Exploratory behaviour and grooming after repeated restraint and chronic mild stress: effect of desipramine Paolo S. D’Aquila ) , Alessandra T. Peana, Vittorio Carboni, Gino Serra Dipartimento di Scienze del Farmaco, UniÕersita degli Studi di Sassari, Via Muroni 23 r a, I-07100 Sassari, Italy ` Received 25 October 1999; received in revised form 19 April 2000; accepted 26 April 2000 Abstract In a previous study, we have recently shown that chronic treatment with desipramine either reduced or potentiated the locomotor response to the dopamine D -like receptor agonist quinpirole, a behavioural response mediated by the mesolimbic dopamine system, 2 Ž depending on whether the animals were subjected, respectively, to repeated restraint or to chronic mild stress different stressors randomly . presented . In this study, we examined the interaction between prolonged exposure to either repeated restraint stress or chronic mild stress with the chronic administration of the antidepressant desipramine on two spontaneous behaviours, in which an involvement of the mesolimbic dopamine system has been suggested: novelty-induced exploratory activity and grooming. Exploratory activity in the open field was reduced by chronic mild stress regardless of the drug treatment, while it was not influenced by restraint stress. Desipramine reduced exploratory activity in rats subjected to restraint stress. Restraint stress increased grooming and desipramine reversed this effect, while increasing grooming in the chronic mild stress group. These findings suggest that antidepressants exert their effect by opposing the modifications induced by stress. The available experimental evidence is consistent with the hypothesis that an important role in the observed behavioural changes is played by the mesolimbic dopamine system. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Antidepressant drug; Desipramine; Grooming; Locomotor activity; Mesolimbic dopamine system; Open field; Restraint stress; Chronic mild stress 1. Introduction Ž . In a recent study D’Aquila et al., 1997 , we observed that exposure of rats to two different stress regimes influ- enced in an opposite manner the effect of chronic treat- ment with the tricyclic antidepressant desipramine on the locomotor response to the dopamine D -like receptor ago- 2 Ž . nist quinpirole Sokoloff et al., 1992 , a behavioural re- sponse mediated by the stimulation of dopamine receptors Ž . in the mesolimbic dopamine system Kelly et al., 1975 . In particular, chronic treatment with desipramine in rats sub- jected to repeated restraint stress reduced the locomotor response to quinpirole, while in rats exposed to chronic Ž . mild stress see Willner et al., 1992 increased it. In previous studies, repeated restraint and chronic mild stress have been reported, respectively, to increase and to de- ) Corresponding author. Tel.: q 39-079-228739; fax: q 39-079-228712. Ž . E-mail address: dsfpaolo@ssmain.uniss.it P.S. D’Aquila . Ž crease the locomotor response to dopamine agonists see Cabib and Puglisi-Allegra, 1996; Papp et al., 1993; Willner . et al., 1992 . These observations prompted us to suggest that antidepressants influence the mesolimbic dopamine system sensitivity in a direction which is opposite to that induced by stress, at least as far as the neural circuits mediating locomotor activity are concerned. On the basis of these observations, we set ourselves the aim to determine whether the bi-directional anti-stress effect of antidepressants detectable by challenging the subjects with a dopamine agonist was paralleled by be- havioural changes under more natural conditions. To explore this possibility, we decided to study the interaction between desipramine and either repeated re- straint or chronic mild stress on a spontaneous behaviour, in which an involvement of the mesolimbic dopamine system has been suggested, i.e. novelty-induced ex- Ž ploratory behaviour in the open field Fink and Smith, . 1980 . Moreover, significant differences between the groups emerged also in the grooming behaviour displayed 0014-2999r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. Ž . PII: S0014-2999 00 00332-0