Abstract:The objective of the present study was to examine the involvement of serotonin 5-HT 2 receptors within the rat nucleus accumbens (Acc) in the regulation of dopamine (DA) release using in vivo microdialysis. Perfusion with the 5-HT 2 agonist (ϩ)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), at concentrations of 25-250 M, through microdialysis probes located in the posterior Acc increased extracellular DA levels to a maximum of 200% of baseline. DOI-induced increases in the extracellular levels of DA were Ca 2ϩ dependent and were inhibited by co-perfusion with the 5-HT 2 antagonist LY-53,857. DOI enhancement of the extracellular concentrations of DA was observed when probes were implanted in the Acc core and shell regions posterior to anteroposterior ϩ1.2 mm from bregma, whereas a small reduction in the extracellular levels of DA was observed in the anterior Acc. There were no differences between core and shell subdivisions within either the anterior or the posterior Acc. These results suggest that activation of 5-HT 2 receptors within the posterior, but not anterior, Acc stimulates DA release, indicating rostral-caudal differences in the interactions of 5-HT with DA systems in the Acc. Key Words: Microdialysis-Dopamine releaseSerotonin 5-HT 2 receptors-(ϩ)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane -LY-53,857. J. Neurochem. 75, 1625-1633 (2000).The mesolimbic dopamine (DA) pathway from the ventral tegmental area (VTA) to the nucleus accumbens (Acc) is involved in mediating many different motivated behaviors, including cocaine, morphine, and alcohol reinforcement (for review, see Di Chiara, 1995). In addition to the rich DA innervation, serotonergic (5-HT) terminals originating in the dorsal raphe nucleus (DRN) also project to the Acc (Azmitia and Segal, 1978;Li et al., 1989;. Moreover, ϳ20% of 5-HT-immunoreactive terminals in the shell and core of the rat Acc are in direct apposition to catecholamine afferents . This suggests that 5-HT could influence the release of DA in this brain region and may be important in DAcontrolled physiological and behavioral events. There also appear to be rostral-caudal differences in 5-HT fiber densities within the Acc, with significantly greater densities in the middle and posterior portions of the Acc than in the anterior subregion (Zhou et al., 1991).Several studies have shown that activation of the DRN 5-HT system or local 5-HT receptors facilitates DA release in the Acc. Yoshimoto and McBride (1992) reported that activating and inhibiting the DRN 5-HT system produced corresponding increases and decreases in the release of 5-HT and DA in the Acc. Electrical stimulation of the DRN enhanced DA release in the Acc but reduced extracellular levels of DA in the striatum (De Deurwaerdere and Spampinato, 1999). Furthermore, activation of 5-HT 3 receptors by local perfusion with 5-HT 3 agonists increased the extracellular levels of DA in the Acc (Chen et al., 1991;Campbell and McBride, 1995). In addition, Parsons and Justice (1993) have shown that local perfusion of 5...
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