Lateral hypothalamic GABA A receptors are involved in the acquisition of the conditioned taste aversion

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ABSTRACTS

Transient Declines in Blood Glucose Precede Increased Hunger Ratings in Humans. L. A. CAMPFIELD, F. J. SMITH, M. ROSENBAUM and J. HIRSCH. HoffmannLa Roche, Nutley, NJ 07110 and Rockefeller University, New York, NY 10021, U.S.A. The physiological basis for hunger and meal initiation in humans have been the subject of extensive research and debate for many decades. Our aim was to determine if meal requests (MR) and changes in hunger ratings (AHR) in humans were related to spontaneous changes in blood glucose (BG). In our first study, BG was continuously monitored on-line and visual analog HR and MR were recorded following an overnight fast. In 83% of the 18 subjects, both HR and MR were preceded by, and significantly correlated with, brief, spontaneously resolving transient declines in BG (nadir:- 10% at 27 min) (TDBG). This association is being tested in a second study using insulin to mimic spontaneous TDBG. Each subject was studied twice: either insulin or saline was infused while HR were obtained. Preliminary results in five subjects indicate that HR increased after induced TDBG. These results suggest that TDBG reflect an antecedent physiological event or provide a signal related to the expression of hunger in humans.

Lateral Hypothalamic GABA A Receptors are Involved in the Acquisition of the Conditioned Taste Aversion. R. CAULLIEZ and S. NICOLAIDIS. Neurobiologie des Regulations, CNRS URA 7860, College de France, 11 pl. M. Berthelot, 75231 Paris, France. Previous experiments showed that electrolytic lesions of the lateral hypothalamic area (LHA) disrupt the acquisition of a conditioned taste aversion (CTA). We investigated the effect of tetrodotoxin (non-specific neuronal activity blocker), bicuculin (GABA-A receptor antagonist), sulpiride (D2-dopaminergic receptor antagonist) or vehicle on the acquisition of CTA. Male Wistar rats were bilaterally implanted with microinjection canula in the LHA, and trained to drink for half an hour per day. The microinjections were performed at the end of the drinking session of a 0.1% saccharin solution and 10 min before the negative reinforcement by lithium chloride i.p. injection. Saccharin CTA strength was evaluated in a subsequent drinking session. Only tetrodotoxin (completely) and bicuculin (partially, i.e. 43%) were effective in disrupting significantly the acquisition of the CTA. These data confirm the implication of LHA in the CTA acquisition and suggest that GABA A but not D2 dopaminergic receptors are involved partially in the processing of the taste illness association. (Supported by MRT SIRET 180089013-00296 APE9311).

Behavioural and Neural Mechanisms for Benzodiazepine-induced Hyperphagia. S. J. COOPER 1, S. HIGGS 1 and P. G. CLIFTON 2. ~School of Psychology, University of Birmingham, Edgbaston, Birmingham B 15 2T~, U.K. and 2Laboratory of Experimental Psychology, University of Sussex, Falmer, Brighton BN1 9QG, U.K. First, we have carried out a meal pattern analysis study with the benzodiazepine receptor (BZR) partial agonist, bretazenil (0"l-l'0mg/kg, i.p.) in freely-feeding adult male hooded rats. The results indicated an initial marked hyperphagic effect present in the first 2-h bin of the night period following bretazenil administration. The size of the first meal doubled after either 0-3 or 1"0 mg/kg bretazenil. Second, we have investigated brainstem sites of action for BZ-induced hyperphagia. Results indicate that direct administration of the water-soluble BZ, midazolam, into the parabrachial nucleus, but not the nucleus of the solitary tract, is sufficient to produce a significant hyperphagic response. This response was blocked by coadministration