Serotonin 5‐HT₂ Receptor Stimulation of Dopamine Release in the Posterior but Not Anterior Nucleus Accumbens of the Rat

Abstract

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...

Fluoxetine Alleviates Behavioral Depression while Decreasing Acetylcholine Release in the Nucleus Accumbens Shell

“…The possibility that local fluoxetine decreases behavioral depression through a dopaminergic mechanism cannot be discounted (Nestler and Carlezon, 2006), because infusion of either 5-HT or a 5-HT 2 receptor antagonist into the NAc has been shown to increase DA outflow (Bowers et al, 2000;Parsons and Justice, 1993). It is interesting to note that acute and chronic fluoxetine treatment via systemic routes given to naïve (non-depressed) rats produced either no changes (Clark et al, 1996;Guan and McBride, 1988;Koch et al, 2002Koch et al, , 2004 or slight reductions (Clark et al, 1996;Ichikawa et al, 1998;Ichikawa and Meltzer, 1995) in DA outflow in the NAc.…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…Corresponding to this latter finding, McBride and colleagues found that reverse dialysis of the 5-HT2 receptor agonist DOI increased DA release in the posterior, but not the anterior, NA (Bowers et al, 2000). These studies implicate receptors localized in the NA in the regulation of mesolimbic DA.…”

A history of caloric restriction induces neurochemical and behavioral changes in rats consistent with models of depression

“…We now can confirm that the previously observed effect was not uniquely influenced by intermittent access to PF, and in fact, was not influenced by PF at all, since it was also observed in HCR rats fed only chow or daily PF and chow. There is a growing body of evidence to suggest functional interactions between 5-HT and dopamine in the nucleus accumbens (Bowers, et al, 2000;De Deurwaerdere, et al, 2004;Kuroki, et al, 2003;Liegeois, et al, 2002;Yan and Yan, 2001). It is possible, therefore, that the 5-HT/dopamine interaction is reflected by the strong correlation in turnover ratios present in rats without HCR.…”