Regional Amines Levels in the Rat-brain Following Intraaccumbens Cholecystokinin and Intraperitoneal Amphetamine Pretreatment

Cholecystokinin octapeptide (CCK8) coexists with dopamine (DA) in a subpopulation of mesolimbic DA neurons including the projections to the nucleus accumbens. In this structure, CCK8 has been reported to exert agonist-like or antagonist-like effects on DA-mediated behaviours and on amphetamine's locomotor-activating effects in rodents. These findings raise the possibility that CCK8 plays a role in modulating the neurochemical mechanisms underlying the effects of DA and amphetamine in the mesolimbic DA, system. The purpose of this study was to determine regional tissue monoamine levels in the rat brain and their modulation following injection of CCK8 in the nucleus accumbens. The same paradigm was used to determine the effects of this octapeptide on changes in amine levels induced by amphetamine administered intraperitoneally. DA, norepinephrine (NE), serotonin (5-HT) and their primary metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured using a reversed-phase ion pair high-pressure liquid chromatography system with electrochemical detection (HPLC-ED). Frontal cortex displayed the highest DOPAC/DA ratio and the lowest DOPAC/HVA ratio in contrast to the olfactory tubercle. The intraperitoneal injection of amphetamine (1 mg/Kg) followed by the intra-accumbens administration of 0.15M saline decreased the levels of DOPAC and increased DA, 5-HT and 5-HIAA both in nucleus caudatus and nucleus accumbens. The DA agonist induced a decrease in the level of NE in olfactory tubercle and frontal cortex. The direct administration of CCK8 (300 pmol) into the nucleus accumbens decreased the level of DA, DOPAC and 5-HT mainly in olfactory tubercle and nucleus accumbens itself. In nucleus caudatus, the same injection of the octapeptide increased the level of these amines supporting the view that CCK8 exerts opposite action in the dorsal and ventral parts of the striatum. CCK8 produced minor effects in frontal cortex, decreasing the levels of NE and 5-HT and increasing 5-HIAA without any action on DA, DOPAC and HVA. Finally, when combined with intraperitoneal amphetamine (1 mg/Kg), intra-accumbens CCK8 (300 pmol) failed to potentiate or to antagonize the amphetamine-induced effects on DA and its metabolites suggesting that, in the rat brain, the octapeptide does not display dopamine agonist-like or antagonist-like effects in any of the regions studied