Different effect of desipramine on locomotor activity in quinpirole-treated rats after repeated restraint and chronic mild stress

We have studied the effect of chronic treatment with the tricyclic antidepressant drug desipramine on locomotor activity in rats challenged with the administration of the D2-like dopamine agonist quinpirole, after prolonged exposure to two different stress regimens, repeated restraint stress and chronic mild stress (different stressors randomly presented). These stress schedules have been previously reported to influence in opposite ways the sensitivity to the locomotor response mediated by the stimulation of mesolimbic dopamine receptors. In particular, repeated restraint has been reported to induce an increased response to the locomotor effect of amphetamine, while chronic mild stress has been reported to induce a decreased locomotor response to quinpirole. In the present study, repeated restraint stress failed to influence the locomotor activity after challenge with quinpirole, while chronic mild stress reduced this response. Chronic treatment with desipramine failed to influence this response in the control group, but exerted opposite effects in the two stressed groups. In particular, chronic desipramine reduced locomotor activity in quinpirole-treated rats in the restraint stress group, and increased it in the chronic mild stress group, thus preventing the subsensitivity induced by this stress regimen. The present results, taken together with results from earlier studies, are consistent with the hypothesis that the effect of antidepressants on the sensitivity of the mesolimbic dopamine receptors mediating the locomotor behavioural response tends to be opposite with respect to that exerted by stress, regardless of its direction. However, since we failed to show an increased locomotor activity after quinpirole challenge in the repeated restraint group, this hypothesis remains to be demonstrated. The two stress schedules reduced body weight gain in a similar way, therefore their different effects do not seem to be due to a difference in stress severity. Thus, the observation that both stress schedules reduced body weight gain in a similar way, but only chronic mild stress reduced the sensitivity to the locomotor response to quinpirole, shows that this effect is not an artefact of body weight decrease.