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Investigates the antidepressant-like effects of agomelatine, melatonin and the neurokinin1 receptor antagonist GR205171 in impulsive-related behavior in rats. Neurobiological mechanisms responsible for this effect; Binding affinities of melatonin and agomelatine at cloned human receptor subtypes; Effects of melatonin and agomelatine on food intake.

Rationale: Dopaminergic mechanisms are thought to be critically involved in reward-related processes and seeking behaviour. Objective: To examine the involvement of dopamine in seeking behaviour supported by a natural reinforcer, food, and assess the role of D[sub 2] and D[sub 3] receptor subtypes in food-seeking, using an operant reinstatement procedure. Methods: Wistar rats were subjected to a within-session extinction procedure. Experimental sessions consisted of a 15-min rewarded period during which each fight lever press delivered one food pellet and initiated a 10-s time out period (FR1:TO[sub 10s]), followed by a 45-min extinction period during which responding was no longer rewarded. The reinstating effects of dopaminergic drugs, food priming, or the combination of both treatments, were investigated during spaced test sessions. In dose range studies, dopamine receptor ligands were administered 20 or 30 min into the test sessions. In interaction studies, antagonists were injected immediately before testing. Food priming consisted of two pellets non-contingently delivered 45 min into the test sessions. Results: Well trained rats emitted many responses during the rewarded period but almost none during extinction. During the last 15 min of the test sessions, non-rewarded responding was reinstated by the D[sub 2]/D[sub 3] agonist, apomorphine (0.1250.25 mg/kg, SC), and the D[sub 3] preferring agonist, 7-OHDPAT (2-4 mg/kg, SC), but not by quinelorane (0.0042 mg/kg, SC), another D[sub 3] preferring agonist. In interaction studies, the D[sub 2] preferring antagonist, raclopride (0.06-0.125 mg/kg, IP), and the D[sub 3] preferring antagonist, l-nafadotride (1 mg/kg, IP), counteracted the reinstating effect of apomorphine and 7-OH-DPAT. Pellets noncontingently delivered during extinction, reinstated modest, but significant, responding. Such food-primed foodseeking was altered by neither nafadotride (0.015-1 mg/ kg, IP) nor the D[sub 2]/D[sub 3] antagonists,... [ABSTRACT FROM AUTHOR]