PII S0361-9230(97)00211-6 Testosterone, Preoptic Dopamine, and Copulation in Male Rats ELAINE M. HULL, 1 JIANFANG DU, DANIEL S. LORRAIN AND LESLIE MATUSZEWICH Department of Psychology, Park Hall, State University of New York at Buffalo, Buffalo, NY 14260, USA ABSTRACT: Steroid hormones prime neural circuits for sex- ual behavior, in part by regulating enzymes, receptors, or other proteins affecting neurotransmitter function. Dopamine facilitates male sexual behavior in numerous species and is released before and/or during copulation in three integrative neural systems. The nigrostriatal system enhances readiness to respond; the mesolimbic system promotes many appeti- tive behaviors; the medial preoptic area (MPOA) contributes to sexual motivation, genital reflexes, and copulation. We have reported a consistent relationship between precopula- tory dopamine release in the MPOA, when an estrous female was behind a perforated barrier, and the ability to copulate after the barrier was removed. Recent, but not concurrent, testosterone was necessary for the precopulatory dopamine response and copulation. The deficit in MPOA dopamine re- lease in castrates was observed in basal conditions as well as the sexual context. However, dopamine in tissue punches from castrates was higher than in intact males. Because tissue levels represent primarily stored neurotransmitter, do- pamine appeared to have been synthesized normally, but was not being released. Amphetamine induced greater dopamine release in castrates, again suggesting excessive dopamine storage. The decreased release may result from decreased activity of nitric oxide synthase in the MPOA of castrates. A marker for this enzyme showed lower activity in castrates than in intact males. Finally, blocking nitric oxide synthase in intact males blocked the copulation-induced release of do- pamine in the MPOA. Therefore, one means by which testos- terone may promote copulation is by upregulating nitric ox- ide synthesis in the MPOA, which in turn enhances dopamine release. © 1997 Elsevier Science Inc. KEY WORDS: Nitric oxide, MPOA, Microdialysis, HPLC-EC. STEROID PRIMING OF NEURAL CIRCUITS Genomic actions of steroid hormones prime neuronal circuits that regulate sexual behavior in most mammals. However, hormonal effects on gene transcription are relatively slow and long lasting, whereas the complex cascade of copulatory behavior is rapidly executed and intricately coordinated with a partner. Hormones facilitate sexual behavior by biasing sensorimotor integration, so that a sexually relevant stimulus is more likely to elicit a sexual response. The means by which hormones prime specific neural circuits undoubtedly includes the up (or down) regulation of neu- rotransmitter synthesis, release, receptors, or other proteins that affect neurotransmitter function. ROLES OF DOPAMINE IN MALE SEXUAL BEHAVIOR One candidate for a central role is dopamine, because dopa- minergic drugs have long been known to facilitate masculine, and probably also feminine, sexual behavior (reviewed in [2,25]). Dopamine is released in several key integrative sites. A common feature of dopaminergic action is enhancement of sensorimotor function, probably achieved by removing tonic inhibition [5]. Thus, steroid hormones may prime neurons to be responsive, but the neurons cannot respond fully unless the tonic inhibition is first removed (Fig. 1). Therefore, dopamine does not elicit behavior directly, but al- lows stimuli to have easier access to hormonally primed output pathways. Dopamine’s short-term biasing is similar to the longer term biasing of steroid hormones, in that certain neuronal circuits may be preferentially facilitated. This preferential facilitation may enable the expression of the hormonal effects. Three major integrative systems control sexual motivation and genital and somatomotor responses in male rats [12] (Fig. 2). A key factor in this model is that sensory input from a receptive female, and/or the act of copulation, elicits the release of dopamine in each of these systems [3,15,23]. The largest system, innervated by the nigrostriatal dopamine tract, enhances the initiation and execution of movements. Degeneration of this tract in Parkinson’s disease results in difficulty initiating movements, slowness of actions, and tremor. Therefore, the nigrostriatal system is thought to contribute to the somatomotor patterns of pursuit and mounting of the female [36]. The second system, innervated by the mesolimbic dopamine tract, is critical for appetitive behavior and reinforcement. It has been implicated in feeding, drinking, brain stimulation reward, drug addiction, sexual behavior, and active avoidance of noxious stimuli (reviewed in [3,4,26,35,37]). Blocking dopamine receptors in the nucleus accumbens, a major terminal of this tract, decreased anticipatory level changing in search of a female in a bilevel apparatus [33]. Conversely, stimulating dopamine receptors in the same area restored conditioned lever press responding for a fe- male, which had been disrupted by lesions of the amygdala [10]. However, both lever pressing and level changing are composite measures that confound specifically sexual motivation with motor activity and general motivational arousal. An X-maze (also called a plus-maze) allows dissociation of these measures. A receptive female and a stud male are in opposite goal boxes, and the other two goal boxes are empty. The male is placed into the center of the apparatus and must run to one of the four goal boxes. Sensorimotor activation (speed of running to any goal box or number of trials in 1 To whom requests for reprints should be addressed. Brain Research Bulletin, Vol. 44, No. 4, pp. 327–333, 1997 Copyright © 1997 Elsevier Science Inc. Printed in the USA. All rights reserved 0361-9230/97 $17.00 + .00 327