Sexual behavior induction of c-Fos in the nucleus accumbens and amphetamine-stimulated locomotor activity are sensitized by previous sexual experience in female Syrian hamsters

Abstract

Dopamine transmission in the nucleus accumbens can be activated by drugs, stress, or motivated behaviors, and repeated exposure to these stimuli can sensitize this dopamine response. The objectives of this study were to determine whether female sexual behavior activates nucleus accumbens neurons and whether past sexual experience cross-sensitizes neuronal responses in the nucleus accumbens to amphetamine. Using immunocytochemical labeling, c-Fos expression in different subregions (shell vs core at the rostral, middle, and caudal levels) of the nucleus accumbens was examined in female hamsters that had varying amounts of sexual experience. Female hamsters, given either 6 weeks of sexual experience or remaining sexually naive, were tested for sexual behavior by exposure to adult male hamsters. Previous sexual experience increased c-Fos labeling in the rostral and caudal levels but not in the middle levels of the nucleus accumbens. Testing for sexual behavior increased labeling in the core, but not the shell, of the nucleus accumbens. To validate that female sexual behavior can sensitize neurons in the mesolimbic dopamine pathway, the locomotor responses of sexually experienced and sexually naive females to an amphetamine injection were then compared. Amphetamine increased general locomotor activity in all females. However, sexually experienced animals responded sooner to amphetamine than did sexually naive animals. These data indicate that female sexual behavior can activate neurons in the nucleus accumbens and that sexual experience can cross-sensitize neuronal responses to amphetamine. In addition, these results provide additional evidence for functional differences between the shell and core of the nucleus accumbens and across its anteroposterior axis.

Fig. 1.

Nucleus accumbens tissue sections stained for calbindin-D and c-Fos. A–C are sections from the rostral (A), middle (B), and caudal (C) nucleus accumbens stained (midline is left) for calbindin, illustrating the division between the shell and core subregions (asterisks). There are 320 μm between the rostral and middle sections and 240 μm between the middle and caudal sections. The bottom images (D, E) are examples of c-Fos staining from the caudal core (D) and shell (E) of the nucleus accumbens (midline is right) of a sexually experienced female killed after a sexual behavior test. Therectangle illustrates the sampling area (0.2 × 0.5 mm).

Fig. 2.

c-Fos expression in the shell and core of the nucleus accumbens at the rostral, middle, and caudal levels for each of the treatment groups. A three-way ANOVA (treatment times rostral–caudal level times shell–core) was used to examine the effects of sexual experience and behavior on the mean ± SEM number of c-Fos cells. No significant main effects of treatment and no three-way interaction among treatment, accumbens level, and shell–core were found.

Fig. 3.

c-Fos expression in the shell and core of the nucleus accumbens, collapsed across the rostral–caudal level. The three-way ANOVA revealed a two-way interaction between treatment and mean ± SEM number of c-Fos cells in the shell and core of the nucleus accumbens (treatment times shell–core;F_(2,24) = 4.243; p< 0.026). A one-way ANOVA probing this interaction found significant main effects of the treatment groups only in the nucleus accumbens core (F_(2,24) = 7.341; p< 0.003) and not in the shell of the accumbens (F_(2,24) = 1.271; p> 0.1). Different letters indicate significant differences between groups.

Fig. 4.

c-Fos expression through the rostral–caudal dimension of the nucleus accumbens, collapsed across the core and shell. Although a three-way ANOVA indicated that the two-way interaction between treatment groups and the mean ± SEM number c-Fos cells through the rostral–caudal levels of the nucleus accumbens only approached significance (F_(4,48) = 2.365; p < 0.066), we probed each level of the nucleus accumbens separately for an effect of treatment on c-Fos staining. A one-way ANOVA revealed significant main effects of the treatment groups in both the rostral level (F_(2,48) = 5.230; p< 0.009) and caudal level (F_(2,48) = 7.455; p < 0.002) but not in the middle level (F_(2,48) = 1.744; p> 0.1) of the nucleus accumbens. Different lettersindicate significant differences between groups.

Fig. 5.

Effects of amphetamine on the general activity of sexually experienced and sexually naive female hamsters. A two-way ANOVA (treatment times testing period) revealed an interaction between treatment group and testing period (F_(12,150) = 2.288;p < 0.011) for mean ± SEM activity counts. A one-way ANOVA probing the individual treatment groups showed significant changes in the general activity for females in the experience/amphetamine (F_(6,150) = 3.0468; p < 0.008) and no experience/amphetamine (F_(6,150) = 3.893;p < 0.001) treatment groups. The activity of the females injected with saline did not change (F_(6,150) = 1.619;p < 0.1). Post hoc tests indicated that the sexually experienced females responded more rapidly to amphetamine, showing an increase in activity within the first 10 min after injection. Sexually naive females did not respond to the amphetamine until 20 min after injection. *p < 0.05 versus the period before testing.