Involvement of prefrontal dopamine neurones in behavioural blockade induced by controllable vs uncontrollable negative events in rats.

The present study was undertaken to investigate the involvement of dopaminergic (DA) neurones afferent to the prefrontal cortex in stress-related behaviours induced by controllable vs uncontrollable negative events. Rats were either sham-operated or given a bilateral infusion of 6-hydroxydopamine (4 micrograms in 0.4 microliter) into the prefrontal cortex which resulted in a specific and almost complete (80%) reduction of local DA. Three weeks after surgery, sham and lesioned rats were subjected to one of the following experimental procedures involving (1) controllable or (2) uncontrollable events: (1) the punished drinking test and a FR1/FR7 schedule of food/shock presentation; (2) the forced swimming test and the learned helplessness paradigm. DA depletion in the prefrontal cortex resulted in an increase in punished responding in the drinking test and under the FR schedule; the anti-punishment effects of diazepam (2 mg/kg) were not modified. Lesions also induced a reduction in immobility duration in the forced swimming test but failed to affect the induction of escape deficits in rats trained for learned helplessness. In the latter two models, DA depletion in the prefrontal cortex did not modify the antidepressant effects of desipramine (32 mg/kg and 24 mg/kg/day, respectively). These results suggest that controllable and acute aversive situations may be modulated by DA neurones in the prefrontal cortex. DA neurones, however, may not be crucial in the modulation of delayed and uncontrollable stress-related behaviours. Taken together, the present findings suggest that an increased tendency to perseverate could be the main behavioural feature associated with DA lesion in the prefrontal cortex. Acute vs delayed consequences of negative events could be an additional relevant factor for the involvement of DA neurons in stress-related behaviours.