Sex, drugs and gluttony: how the brain controls motivated behaviors

Abstract

Bart Hoebel has forged a view of an integrated neural network that mediates both natural rewards and drug use. He pioneered the use of microdialysis, and also effectively used electrical stimulation, lesions, microinjections, and immunohistochemistry. He found that feeding, stimulant drug administration, and electrical stimulation of the lateral hypothalamus (LH) all increased dopamine (DA) release in the nucleus accumbens (NAc). However, whereas DA in the NAc enhanced motivation, DA in the LH inhibited motivated behaviors. The Hull lab has pursued some of those ideas. We have suggested that serotonin (5-HT) in the perifornical LH inhibits sexual behavior by inhibiting orexin/hypocretin neurons (OX/HCRT), which would otherwise excite neurons in the mesocorticolimbic DA tract. We have shown that DA release in the medial preoptic area (MPOA) is very important for male sexual behavior, and that testosterone, glutamate, nitric oxide (NO) and previous sexual experience promote MPOA DA release and mating. Future research should follow Bart Hoebel's emphasis on neural systems and interactions among brain areas and neurotransmitters.

Fig. 1

Temporal changes in extracellular serotonin (5-HT) collected from the lateral hypothalamus of male rats before and during copulation. Each data point is the mean (±SEM) for 6-min dialysate samples collected during baseline (B), in the presence of an estrous female (F), during copulation (C), during the post-ejaculatory interval (P), and after the female was removed (expressed as % of mean baseline levels). 5-HT levels increased during the second (P2) and third (P3) postejaculatory intervals, compared to the final baseline. 5-HT during P3 was also higher than in the fourth copulatory interval. Samples collected during the second and third copulation series were not analyzed, because most males ejaculated before a full 6-min sample could be collected. The summary graph (inset) shows the mean (± SEM) for data for the 15 sample periods collapsed into five groups, based on behavioral condition. Samples collected during post-ejaculatory intervals showed higher 5-HT levels than all other conditions. (Figure from [8] with permission.)

Fig. 2

Testosterone-mediated enhancement of sexual activity may occur in part through increased DA release in the MPOA. Gonadally intact male rats showed an increase in extracellular DA during precopulatory exposure to an inaccessible estrous female, and all intact males then copulated when the female was placed in their cage. Males castrated 2 weeks before showed no DA release in response to the female, and none copulated. Two thirds of 1-week castrates copulated and showed the DA increase, whereas the remaining third did not copulate and did not show a DA increase. *P<.05, compared to baseline for testosterone-treated castrates; **P<.01, compared to final baseline for intact males or for one-week vehicle-treated castrates that copulated; +P<.05, compared to final baseline for vehicle-treated castrates that failed to copulate. (Reprinted from Ref. [22] with permission.)

Fig. 3

Lesions of the medial amygdala inhibit the release of DA in the MPOA resulting from exposure to an estrous female and copulation. Levels represent % changes from baseline (BL) in response to precopulatory exposure to an estrous female (PRE), during copulation (C1 – C3) and after copulation (POST). Extracellular DA significantly increased during the precopulatory and copulatory stages of testing for animals with sham lesions but not for animals with MeA lesions. Values are expressed as mean ± SEM. *P<.05; **P<.01. (Reprinted from [37] with permission.)

Fig. 4

Levels of DA in dialysate from the MPOA of animals receiving MeA stimulation or vehicle microinjection. Levels represent % change from baseline (BL) in response to MeA-stimulation or vehicle microinjection; samples collected after microinjections into the MeA are post-injection samples 1 – 6 (P1 – P6). Levels of extracellular DA significantly increased after MeA microinjections for animals receiving MeA stimulation but not for animals receiving vehicle. Values are expressed as mean ± SEM. (*P<.05) (Reprinted from [38] with permission.)