Sexual experience sensitizes dopamine pathways in female Syrian hamsters
Abstract
Repeated exposure to addictive drugs produces neurochemical and structural adaptations in mesolimbic dopamine neurons. It is known that natural motivated behaviors (e.g. feeding, mating) also activate the mesolimbic dopamine pathway. Before the mechanisms underlying drug addiction can be understood, it is necessary to understand the normal functioning of these brain pathways. The objective of this study was to investigate the sensitization of the mesolimbic dopamine pathway by previous sexual experience in female Syrian hamsters. It was shown that sexual behavior testing increased the number of c-Fos immunoreactive cells in the nucleus accumbens and that this c-Fos labeling was augmented by previous sexual experience. These results provide further evidence that repeated sexual behavior testing sensitizes this dopamine pathway. Moreover, sexual experience cross-sensitizes neuronal responses to amphetamine, implying there are common mechanisms of action for drugs and natural motivated behaviors. These sensitized increases in cellular activity appear to be partly mediated through the D1 dopamine receptor. Sexual experience increased D 1 receptor mediated adenylate cyclase activity in the nucleus accumbens of female Syrian hamsters. However, analysis of mRNA expression in the nucleus accumbens with DNA microarrays showed that the expressions of many functional proteins are altered with previous sexual experience. One functional consequence of these sensitized changes produced by previous sexual experience is regulation of the rate of copulatory contact by sexually naive male hamsters. Mating sexually naive male hamsters with experienced females increased the copulatory efficiency of the naive males compared to when they were paired with sexually naive females, an effect that persisted for at least 6 weeks. Furthermore, these changes in copulatory behavior are dependent on basal forebrain dopamine activity. Damaging these dopamine neurons in the female hamster with the selective catecholamine neurotoxin 6-hydroxydopamine blocked the effects of female sex experience on naive male hit rate. This research provides new information about the activation of brain reward mechanisms by natural motivated behaviors. Since the mesolimbic dopamine pathway is responsive to both behaviors that are part of the natural repertoire of an animal and to certain drugs of abuse, this research may offer insights into the development of addiction in humans.
Degree
Ph.D.
Advisors
Meisel, Purdue University.
Subject Area
Neurology|Psychobiology|Anatomy & physiology|Animals
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