Dissociation of receptor sensitivity changes in rat perifornical hypothalamus: a role for dopaminergic receptors in amphetamine anorexic tolerance.

Development of a contingent tolerance to amphetamine (AMPH) anorexia has been reported with chronic s.c. injections in rats (Ghosh and Parvathy, 1973, 1976). Using this model, the present study examined the role of potential receptor sensitivity changes in the beta adrenergic and/or dopamine (DA) receptors in the perifornical hypothalamus (PFH) during chronic central and peripheral drug injections. Chronic injections of AMPH into the PFH, or l-dopa injected s.c., resulted in persistent anorexia in the daily first 2 hr of eating on all test days compared with the next 2 hr that showed a progressive increase in eating with subsequent injections, the net effect being an apparent tolerance to its 4 hr anorexic effect. The tolerance patterns obtained with these two treatments were essentially the same as that of s.c. AMPH, suggesting a role for PFH catecholamine synapses, particularly at the postsynaptic receptor level. Selective beta adrenoceptor-mediated anorexia, as obtained with chronic PFH-injected nor-adrenaline and isoprenaline, was dose-dependent and persistent on all days, suggesting that no change in the sensitivity of PFH beta adrenoceptors had occurred. This contrasted with the PFH-injected DA, which produced a rapid tolerance development due to a progressive loss of effect in the first 2 hr. Present findings suggest that although beta adrenergic and DA mechanisms act in concert in eliciting the acute anorexic effects of AMPH, DA, rather than beta adrenergic system, has a predominant influence in the development of tolerance to the anorexic effect of AMPH.