Reversal of a reward system by dexfenfluramine

ABSTRACTS

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attenuated the inhibitory responses to both DR stimulation and electrophoretic 5HT application. Seventy-three (25%) were excited by DR stimulation, and 71% of these were glucose insensitive neurons. Methysergide attenuated the excitatory responses to DR stimulation and the inhibitory response to electrophoretic 5HT, but (-)-propranolol did not attenuate the excitation. Intracellular recordings during DR stimulation showed monosynaptic EPSPs or IPSPs with 3.8 and 3.0 msec latency, respectively. The reversal potential for the former was - 17 and for the latter, -94mV. Tnus we concluded that 75% of LHA glucose-sensitive neurons receive inhibitory 5HT inputs from the DR through 5HT 1 receptors, and 20% of glucoseinsensitive neurons receive excitatory inputs from the DR through 5HT 2 receptors though 41% of these receive inhibitory inputs through 5HT 1 receptor. Reversal

of a Reward System by Dexfenfluramine. J. J. ROBERT, M. OROSCO, C. ROUCH, C. JACQUOT and Y. COHEN. Laboratoire de Pharmacologic, Facultt5 de Pharmacie, 92290 Chdtenay- Malabry, France. Rats expecting to receive a highly palatable food as a reward, display an increase in nociceptive thresholds. We found that this expectation was related to increases in hypothalamic serotonin and plasmatic /?-endorphin. Dexfenfluramine (1.5 mg/kg, i.p.) partially cancelled this expectation without reversing the increases in serotonin and fi-endorphin. Another mechanism, possibly dopaminergic, might be proposed. It must be noted that dexfenfluramine alone displayed an analgesic action in normal rats. However, in rats expecting a reward, the blockade of this expectation was the stronger effect. This may favour the therapeutic use of dexfenfluramine in patients, not necessarily overeating, but with mood disorders leading to a propensity to snacking.

Is Dopamine (DA) in the Lateral Hypothalamus (LH) Involved in the Inhibitory Regulation of Exploratory Behavior Related to Food and Water Seeking? M. A. PARADA, L. HERNANDEZ and 0. G. HOEBEL. Laboratorio de Fisiologia de La Conducta, Universidad de 10s Andes, Venezuela and Department of Psychology, Princeton University, CA, U.S.A.

Previous experiments showed that bilateral injections of sulpiride in the perifornical area of the lateral hypothalamus (i.p.f. injections) attenuated the anorexia produced in food deprived rats by i.p.f. injections of amphetamine, and elicited feeding and drinking in satiated rats. Those facts suggested an inhibitory role, on feeding and drinking, for dopaminergic D2 receptors in the LH. During those experiments it was evident that sulpiride induced a state of hyperactivity characterized by sniffing, rearing and locomotion which are typical components of exploratory behaviors. Some experiments were conducted to assess this motor stimulant effect of bilateral microinjections of sulpiride using circular tilt cages. Sulpiride increased locomotion in male rats, and this effect was replicated four times. The first experiment was aimed to study the time course of rat motility after sulpiride. This effect was evident immediately after the injections and lasted 75 min. A correlation study carried out between the level of activity and different doses of sulpiride (0,2,4,8 and 16 pg/O.5 ~1)showed the effect to be dose-dependent (R = 0.601; t = 3.7; p = OGO12).In pargyline (15 mg/kg) pretreated rats 1Opg of DA administered i.p.f. 5 min before sulpiride reduced the motor stimulant effect of the neuroleptic from 1601.3 + 337.6 counts/30 min, to 742.5 f 180.4 after DA + sulpiride. Under saline the animals performed in this experiment (425.7 f 137.6 counts/30 min). Amphetamine (2Opg/O.5pl), DA alone, Sch-23390 (15/*g), haloperidol and atropine did not modify the locomotion level. After carbachol (5pg) the animals attained a level of hyperactivity (1459.5 + 1465 countsJ30min) similar to that induced by sulpirid (1595.7k365.7) in the same experiment. Since feeding, drinking and exploratory behavior are induced by sulpiride from the same hypothalamic areas, and sulpiride seems to be acting on postsynaptic D2 receptors, it is tempting