Abstract
Modulation of behavioral and neurochemical activities in the mesolimbic and nigrostriatal dopaminergic systems by estradiol (E2) is well known. Dense expression of cocaine- and amphetamine-regulated transcript (CART) mRNA and peptide in the nucleus accumbens (NA) and striatum (ST) are also reported. Whether E2 modulate the stimulatory effects of CART peptide in the mesolimbic and nigrostriatal dopaminergic (DA) systems in female Sprague-Dawley rats was examined in this study. DA neuronal activities were determined by measuring the concentration of DOPAC (3,4-dihydroxyphenylacetic acid), the major metabolite of DA, in the NA and ST by HPLC-ECD. Intracerebroventricular administration of CART peptide increased the DOPAC content of NA and ST in ovariectomized (OVX) priming E, but not in OVX only and E2-BSA (the membrane-impermeable form of E2) treated female rats. However, two days of injections of E2-S (the water-soluble form of E2) can restore the stimulation of CART peptide on NA and ST DOPAC content. Only E2 antagonist blocked the E2 effects, but testosterone antagonists did not. These findings indicate that E2 play a regulatory role in stimulation of the CART peptide in mesolimbic and nigrostriatal DA systems, and suggest that E2 acts through intracellular genomic rather than extracellular non-genomic mechanisms. [J Physiol Sci. 2007;57 Suppl:S140]