miR-15a and miR-16 regulate serotonin transporter expression in human placental and rat brain raphe cells.

The serotonin transporter (SERT) is a key regulatory molecule in serotonergic transmission implicated in numerous biological processes relevant to human disorders. Recently, it was shown that SERT expression is controlled by miR-16 in mouse brain. Here, we show that SERT expression is regulated additionally by miR-15a as well as miR-16 in human and rat tissues. This post-transcriptional regulation was observed and characterized in reporter assays and likewise when endogenous SERT expression was evaluated in human placental choriocarcinoma JAR cells and rat brain raphe RN46A cells - two cell lines that endogenously express SERT. Similar effects for miR-16 to those of miR-15a were found in both human and rat cell lines. The effects of miR-15a and miR-16 were comparable in extent to those originally reported for miR-16 in mice. These findings represent a novel layer of complexity for SERT expression regulation exerted by the mir-15a/16 cluster, whose genes are adjacently located at human chromosome 13q14.3.

Brain stimulation reward is affected by D2 dopamine receptor manipulations in the extended amygdala but not the nucleus accumbens.

This work examines the effects on brain stimulation reward (BSR) of D1 and D2 dopamine receptor manipulations in the sublenticular central extended amygdala (SLEAc) and the nucleus accumbens shell (NAc). Fifty-three male Long Evans rats received medial forebrain bundle stimulation electrodes and bilateral injection guide cannulae aimed at either the SLEAc or the NAc. The rate-frequency paradigm was used to assess drug-induced changes in stimulation reward effectiveness and in response rate following 0.50 microl injections of isotonic saline, 5.0mug of SKF38393 (D1 receptor agonist), 2.0 microg of SCH 23390 (D1 blocker), 10.0 microg of quinpirole (D2 agonist) and 3.0 microg of eticlopride (D2 blocker). The drugs were injected both ipsi- and contralateral to the stimulation site. When injected into the NAc none of the drugs affected either the frequency required to maintain half-maximal responding or maximum response rate. D2 receptor blockade in the SLEAc contralateral to the stimulation site significantly but modestly enhanced both the stimulation's reward effectiveness and response rate while D2 receptor agonism decreased responding. Injections into the SLEAc ipsilateral to the stimulation site were ineffective. These results suggest that dopaminergic neurotransmission in the SLEAc is more important to reward processes than is dopamine in the NAc. We align our findings with past work by considering methodological details and a currently hypothesized role for NAc dopamine in learning behaviors that lead to reward capture.