Norepinephrine and serotonin receptors in the paraventricular nucleus interactively modulate ethanol consumption

Abstract

The homeostatic function of the hypothalamus has long been recognized. In particular, the role of the paraventricular nucleus (PVN) in regulating ingestive behavior has been of interest. Infusions of serotonin and norepinephrine into the PVN are correlated with nutrient selective decreases and increases in consumatory behavior, respectively. Given the wide range of homeostatic functions of the hypothalamus, it is plausible that similar hypothalamic mechanisms may also be involved in the regulation of ethanol intake. This study examined the effects of PVN infusions of serotonin (5-HT) and norepinephrine (NE) on ethanol intake in a 1-hr limited-access two-bottle paradigm. When intake of 6% (v/v) ethanol versus water stabilized, male Wistar rats were implanted with stainless steel guide cannulae aimed at the PVN. After recovery, NE (20, 50, and 100 nmol), 5-HT (5 and 25 nmol), and their combination (NE 50 nmol + 5-HT 5 nmol) were microinjected into the PVN in a volume of 0.5 microliter/side over 1 min. Baseline ethanol intake was approximately 1.0 g/kg and ethanol preference (milliliters ethanol per total milliliters) was approximately 60%. Both 20 and 50 nmol of NE significantly increased absolute ethanol intake by 50% and relative ethanol intake by approximately 30%. Corresponding decreases were observed in water intake. Neither dose of 5-HT when administered alone altered ethanol or water consumption, but the 5-nmol dose of 5-HT attenuated the increase observed after NE (50 nmol) administration. These data demonstrate that NE and 5-HT receptors in the PVN interact in the modulation of ethanol ingestion. This finding suggests that homeostatic regulatory functions of the hypothalamus are involved in ethanol intake, and a perturbation of this system may influence excessive drinking.

Fig. 1

Representation of coronal section of rat brain corresponding to 1.8 mm caudal to Bregma. The shaded areas show the range of injection sites (i.e., injector location) in the PVN. Dye was infused in unanesthetized animals before histological procedures to estimate pattern of drug diffusion. Histological analysis of dye distribution suggested that the microinjections of NE, 5-HT, and their combination spanned the dorsomedial cap, medial parvocellular, lateral magnocelluiar, and ventral regions of the PVN.

Fig. 2

Effects of PVN infusions of NE, 5-HT, and their combination on ethanol intake (A), water intake (B), and relative ethanol intake (C). All bars, including no-injection (N) and vehicle M controls, represent the average intake of n = 10 animals during 1-hr test sessions with ethanol (6% v/v) and water available. Horizontal reference lines are drawn at the mean of the N control value. Error bars represent SE. * indicates significantly different from both N and V control, p < 0.05, Student Newman-Keuls procedure. Comparison of NE (50 nmoi) to combined administration of NE and 5-HT was conducted with paired t test.