The nucleus accumbens and antidepressants: modulation of ergometrine-induced hyperactivity by typical and atypical antidepressants and neuroleptics in rats

Abstract

This study assesses the behavioural significance of the (-)sulpiride binding sites in the rat nucleus accumbens that bind antidepressants with high affinity and neuroleptics with low affinity. The effects were measured by intra-accumbens injections of typical and atypical antidepressants or neuroleptics, either given alone or in combination with ergometrine (1 microgram/0.5 microliter per side) on rat locomotor activity in a familiar environment. In addition, the after-effects of the combined ergometrine-drug treatment upon locomotor activity were analyzed. The antidepressants shared a common profile of effects. Thus, none of the antidepressants significantly altered locomotor activity in naive rats. Moreover, each antidepressant produced after-effects which were similar to those elicited in the acute ergometrine experiments. However, some antidepressants (amitriptyline and zimelidine) potentiated the ergometrine response, while other antidepressants (desipramine, mianserin and clorgyline) attenuated this response. (-)Sulpiride (0.5 microgram) decreased the ergometrine response when given together with ergometrine or 48 h earlier. Haloperidol had to be given in a dose that was 20 times higher than that of (-)sulpiride in order to be effective. Clozapine (1-10 micrograms) failed to alter the ergometrine response when given together with ergometrine. Only (-)sulpiride produced a dose-dependent attenuation of locomotor activity in naive rats. The present data are discussed in terms of the hypothesis that drugs with antidepressive effects mediate their behavioural effects via mesolimbic (-)sulpiride binding sites.