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

Abstract

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.

Antidepressant-Like Effect of D2/3 Receptor-, but not D4 Receptor-Activation in the Rat Forced Swim Test

“…Dopamine is believed to play a critical role in the neurobiology of depression and in the mechanism of action of antidepressant drugs, a hypothesis based on clinical and preclinical observations (Willner, 1983b;Fibiger, 1995;Charney, 1998;D'Aquila et al, 2000b). As stated above, compounds acting as agonists on dopamine D 2 /D 3 receptors, such as bromocriptine, piribedil, pramipexole, and roxindole (Post et al, 1978;Bouras and Bridges, 1982;Willner, 1983a;Borsini et al, 1988;Muscat et al, 1992;Grunder et al, 1993;Willner et al, 1994;Maj et al, 1996b;Corrigan et al, 2000), and compounds that enhance dopamine levels inhibiting selective dopamine reuptake like amineptine, nomifensine, and bupropion (Kinney, 1985;Dalery et al, 1997), have shown antidepressant-like activity in both preclinical models and clinical settings.…”

“…Interestingly, it has been proposed that an increase in dopamine activity induced by chronic antidepressant treatments is one of the mechanisms of action underlying the efficacy of these compounds, since their effects are antagonized by low doses of D 2 /D 3 antagonists (Borsini et al, 1984;Borsini et al, 1985a, b;Pulvirenti and Samanin, 1986;Sampson et al, 1991;Serra et al, 1992;D'Aquila et al, 2000a). Moreover, antidepressant treatments are associated with increased dopaminergic function in the mesolimbic system and increased behavioral response to dopamine agonists (Spyraki and Fibiger, 1981;Maj et al, 1984a, b;Cervo and Samanin, 1987;De Montis et al, 1990;Ainsworth et al, 1998a;D'Aquila et al, 2000bD'Aquila et al, , 2003, which takes place after chronic treatment (2-3 weeks), a period of time that correlates with that necessary for the onset of antidepressant activity in the clinic.…”

Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

“…To take fi rst the behavioural pharmacological observations: CMS-induced anhedonia is associated with decreased place conditioning to DA agonists (amphetamine and quinpirole), and a decrease in the psychostimulant effects of DA agonists (amphetamine and quinpirole) [49,[146][147][148] . By contrast, CMS-induced 'prohedonia' is reported to be associated with increased place conditioning to a DA agonist (cocaine) and increased psychostimulant effects of DA agonists (amphetamine and quinpirole) [142,143,145] .…”

A final common pathway for depression? Progress toward a general conceptual framework

“…Chronic stress and antidepressant treatment, which produce opposite changes in positively motivated behavior, have been shown also to produce a series of opposing changes in receptor and neuronal function in this system. These effects which include alterations in α 1 -adrenergic (Maj and Rogóz, 1999), 5HT1 (Ossowska et al, 2001;Srinivas et al, 2001), 5HT2A (Ossowska et al, 2001;Esposito, 2006), D1 (Ossowska et al, 2001;Huzarska et al, 2006), D2 (D'Aquila et al, 2000), GR and MR (Holsboer, 2001;Schule, 2007) as well as in neurotrophin release (Duman and Monteggia, 2006) and neuronal morphology McEwen, 2003). These multiple correlated effects appear to be the results of a combination of factors including altered neurotransmitter, cytokine, corticosteroid and neurotrophin release (Duman and Monteggia, 2006;Bisagno et al, 2000;McEwen, 2000).…”