Neural Substrates for Sexual Preference and Motivation in the Female and Male Rat YASUO SAKUMA Department of Physiology, Nippon Medical School, Tokyo, Japan Rodents identify a mating partner by using olfactory cues. Female rats in estrus spend a longer time sniffing odors of sexually active males when physical contacts are hampered. Sexually active males are attracted by odors of receptive females. The preference in either sex disappears when the subjects are gonadectomized, an effect reversible by supplement with estrogen or testosterone. Thus, circulating sex steroids determine the odor preference in both sexes. In both sexes, olfactory cues get to the basal forebrain; this area includes the preoptic area (POA), substantia innominata and accumbens, structures with estrogen receptor–positive neurons. In estrous females, neurons in the POA are activated during precopulatory motivational behavior. Lesion in this area practi- cally eliminates sexual preference and diminishes the motivation. An increase in locomotion in females in estrus, which apparently depends on estrogen-sensitive POA projections to the midbrain locomotor region, has been considered to embody enhanced sexual motivation. Key words: odor preference; preoptic area; accumbens; dopamine; ventral tegmental area; estro- gen; orexin; postejaculatory refractoriness; neural circuitry Introduction In the rat, sexual interactions are initiated and paced by females in estrus through patterns of approach to- ward and withdrawal from sexually active males. 1 Es- trogen and progesterone are needed for this procep- tive behavior to occur. 2 Olfactory cues also play a major role in deciding the females’ approach or pref- erence toward sexually active males over orchidec- tomized males. It appears that both main and ac- cessory olfactory systems are involved in the central transmission of multitudes of pheromones, which cause changes in reproductive neuroendocrinology and be- havior by eventually arriving in the preoptic/basal forebrain. 3 Estrous females with a lesion in the pre- optic area (POA) lose their capability to distinguish sexually active males from orchidectomized males in an alternate choice paradigm, together with a decrease in the total time spent sniffing either male (FIG. 1). 4 The decreased time spent sniffing males may reveal the diminished sexual motivation in POA-lesioned fe- males. The main justification for this reasoning is that the lesion of the medial amygdala, a major relay in olfactory transmission, causes loss of ability to distin- Address for correspondence: Yasuo Sakuma, M.D., Ph.D., Department of Physiology, NipponMedical School, Bunkyo, Tokyo 113-8602, Japan. ysakuma@nms.ac.jp guish sexually active males, without affecting the total time sniffing either male. 5 Indeed, certain POA neu- rons change their activity in relation to motivational contexts. 6 Neurons with estrogen receptor, either α or β, are abundant in the POA. 7 POA lesion abolishes procep- tivity, while it promotes the lordosis reflex, the major component of receptive behavior, in estrous females. 2,8 The POA inhibits the receptivity with its dense projec- tion to the ventral tegmental area. 9 Increased locomo- tor activity in female mice 10 or rats 11 in estrus suggests involvement of POA efferent to the midbrain locomo- tor region. 12 The ventral tegmental area is the origin of ascent toward the accumbens, which has been of- ten associated with the motivational aspect of various behaviors. 13 Lesion of the accumbens, however, leaves sexual behavior unaffected in both male and female rats. 14 We must also consider possibile nonspecific ac- tion of dopamine in the accumbens, because dopamine in the accumbens is associated with aversive and appe- titive events, including general arousal and activation of nonspecific motor patterns. 15,16 Although the ac- cumbens activates locomotion, an important denom- inator for the motivational state in the female rat, 12 through its innervation of the POA, 17 female rats car- rying accumbens lesion persist in showing preference to males in a paradigm that does not allow males to touch females. 14 The POA may be an independent entity for this behavior. Ann. N.Y. Acad. Sci. 1129: 55–60 (2008). C  2008 New York Academy of Sciences. doi: 10.1196/annals.1417.009 55