Effects of intra-ventral pallidal injections of a 5-HT2C agonist on spontaneous and meth-induced motor behavior in rats

The ventral pallidum (VP) is involved in the regulation of motor activity, including that induced by stimulants. The VP contains moderate levels of serotonin (5-HT) receptors. 5-HT2C receptors are moderately expressed in the VP and are commonly co-localized with GABA. Activation of 5-HT2C receptors in the VP was predicted to enhance GABAergic activity. As augmentation of GABAergic outputs from the VP is associated with decreases in motor activity, we hypothesized that injection of a 5-HT2C receptor agonist (MK212) into the VP would dose-dependently decrease motor activity. We further hypothesized that a dose of MK212 that was sub-threshold to reducing spontaneous motor activity would be sufficient to attenuate methamphetamine (meth)-induced motor activity. To test this hypothesis, rats were bilaterally implanted with intra-VP canulae (n=18). After recovery from surgery and habituation to automated motor boxes, spontaneous motor activity was measured for 90min following intra-VP sham or MK212 and ip saline. Two studies were executed in a repeated measures design. A pilot study (n=4) tested the effects of 10, 50, 100, and 500ng/0.50mul/side MK212 and a second study (n=14) tested the effects of 0.33, 6.6, and 10ng MK212. Analysis from the first 30min post VP + ip injection resulted in 0.33 and 6.6ng MK212 showing no effect on motor activity, while doses of 10, 50, 100, and 500ng MK212 showed significant decreases in motor activity. The second study also tested the effect of intra-VP 0.33ng MK212 on meth-induced motor activity (0.5mg/kg meth; ip). Though meth-induced motor activity was not significantly decreased by intra-VP 0.33ng MK212, there was a trend suggesting modest attenuation of meth-induced hyperactivity. Since this was the first study to explore 5-HT2C receptor function in the VP, further efforts are required to fully understand this underappreciated brain region in substance abuse.