152 /~ram Resca~,:,~.' -;i~s{l~Jg!)} 152 J5< [-'lscwc~ BRES 23927 Stimulation of the paraventricular nucleus with glutamate activates interscapular brown adi tissue thermogenesis in rats Shimon Amir Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec (Canada) (Accepted 10 October 1989) Key words: Paraventricular nucleus; Glutamate; Brown adipose tissue; Thermogenesis; Energy balance; Rat The paraventricular nucleus (PVN) of the hypothalamus is involved in the control of energy balance in rodents through its influences on feeding, pituitary hormone secretion and the autonomic nervous system. In the present study, selective stimulation of PVN neurons by means of local microinjection of the excitatory amino acid glutamate (100 mM, 500 mM or 1 M, in 100 nl) ted to a concentration-dependent increase in interscapular brown adipose tissue (IBAT) temperature in urethane-anaesthetized rats. This effect could be prevented by pretreatment with the sympathetic ganglionic blocker, chlorisondamine chloride, or the fl-adrenergic receptor antagonist, propranolol, but not by hypophysec- tomy, implicating the involvement of the sympathetic outflow. Thermogenesis in brown adipose tissue (BAT) is an important accompaniment of overfeeding in small mammals, and previous studies have shown that signals generated in response to feeding gain access to the PVN. The present finding that direct activaton of PVN neurons stimulates thermogenesis in BAT, taken together with data that the PVN receives dietary signals from the gut, support the view that PVN neurons may function in monitoring the balance between energy intake and its expenditure. In addition to its role in the control of feeding and pituitary hormone secretion 14'~7'z9, the paraventricular nucleus of the hypothalamus (PVN) is implicated in the regulation of the autonomic nervous system. PVN neu- rons project to sympathetic and parasympathetic nuclei in the brainstem and spinal cord 22"27'29, and studies have shown that electrical or chemical stimulation or lesions in the PVN modify the autonomic outflow and affect autonomic functions such as arterial pressure and heart rate in experimental animals 2'3'11'21'3°. More recently, evidence has been presented for a possible involvement of the PVN in the control of thermogenesis in brown adipose tissue (BAT). Heat generation in BAT is stim- ulated by the sympathetic system via release of nor- epinephrine 12"27, and it has been shown that electrical stimulation of the PVN 5 or intra-PVN injection of the neuropeptide corticotropin-releasing factor (CRF) 13 in- crease interscapular BAT (IBAT) temperature in rats. In the present study we sought to further examine the involvement of the PVN in the control of BAT thermo- genesis by evaluating the effect on IBAT temperature of selectively stimulating PVN neurons with the excitatory amino acid glutamate 6. To study the effect on BAT thermogenesis of injecting glutamate into the PVN, normally fed male Wistar rats (270-320 g) were anaesthetized intraperitoneally with urethane (1.4 g/kg) at the beginning of the 12-h lights-on period and mounted in a stereotaxic instrument equipped with a thermostatically-controlled heating blanket cali- brated to keep body temperature above 36 °C. A small incision was made 5 cm posterior to the scapulae and a thermistor probe (YSI 409B) was inserted and placed under the right lobe of interscapular BAT. A second thermistor probe (YSI 401) was inserted 5 cm into the rectum. A 28-gauge needle connected to a Hamilton microsyringe containing saline or sodium glutamate (pH 7.0) was then introduced into the right PVN using the following coordinates from the Paxinos and Watson 2° atlas: AP -1.6, L 0.2, V 7.9-8.1. The position of the injection needles was later verified histologically. IBAT and core temperatures were monitored continuously using YSI telethermometers (model 41) connected to a flat bed recorder. Injection of sodium glutamate (100 nl of 0.1, 0.5 or 1 M) into the PVN produced a sharp, concentration- dependent increase in IBAT temperature, which was maximal at 6-15 min and returned to preinjection value 20-30 rain later (Figs. 1 and 2). Injecting saline (100 nl) into the PVN had no effect on IBAT temperature. Intra-PVN glutamate, though not saline, also increased core temperature; however, the change in core temper- ature was much less pronounced and never exceeded the increase in IBAT temperature (Fig. 1). PVN neurons project to the median eminence and Correspondence: S. Amir, Department of Psychology, Concordia University, 1455 deMaisonneuve Boulevard West, Montreal, Quebec H3G 1M8, Canada. 0006-8993/90/$03.50 (~) 1990 Elsevier Science Publishers B.V. (Biomedical Division)