Differential effects of melanin concentrating hormone on the central dopaminergic neurons induced by the cocaine- and amphetamine-regulated transcript peptide

Stimulatory effects of cocaine- and amphetamine-regulated transcript (CART) peptide on central mesolimbic, nigrostriatal and mesocortical dopaminergic (DA) neurons were examined in female Sprague-Dawley rats. We also determined the different blocking effects of melanin concentrating hormone (MCH) on the stimulation by CART peptide in central DA systems. Intracerebroventricular administration of 1 mug CART peptide (55-102) produced increases in 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens (NA) at 15 and 45 min, and in the striatum (ST) at 15 min, but not in the medial prefrontal cortex (MPFC). We found that the agonist of alpha-melanocyte stimulating hormone (alpha-MSH), MT II, at 10 mug had a stimulatory effect on the NA and ST DOPAC levels similar to the CART peptide. In contrast, 1 mug MCH and the antagonist of alpha-MSH, HS014, significantly decreased NA and ST DOPAC levels. However, only MCH prevented the stimulatory effect of CART peptide on DOPAC levels in the NA, but not in the ST. These results indicate that the stimulation of CART peptide on central DA neurons is region-specific, and that this effect can be blocked by MCH but not by the antagonist of alpha-MSH.