Evidence of a functional relationship between the nucleus accumbens shell and lateral hypothalamus subserving the control of feeding behavior

Inhibition of neurons in the nucleus accumbens shell (AcbSh) with local injections of GABA agonists or glutamate antagonists elicits an intense, but specific, feeding response resembling that seen after stimulation of the lateral hypothalamus (LH). To help characterize the contribution of the LH to the expression of AcbSh-mediated feeding, we used the immunohistochemical detection of the nuclear protein Fos to determine whether inhibition of AcbSh cells results in an activation of LH neurons. Injections of the GABA(A) agonist muscimol into the AcbSh greatly increased the number of cells exhibiting Fos-like immunoreactivity in the LH, as well as in the lateral septum, paraventricular hypothalamic nucleus, ventral tegmental area, substantia nigra pars compacta, and nucleus of the solitary tract. Blocking activation of LH neurons with the selective NMDA receptor blocker D(2)-AP-5 is known to suppress deprivation-induced feeding. We found that injections of D(2)-AP5 into the LH also dose-dependently suppressed AcbSh-mediated feeding. It is likely that inhibition of GABAergic neurons in the AcbSh is responsible for eliciting this feeding. If a behaviorally relevant GABAergic projection terminates in the LH, we should be able to mimic the effects seen after inhibition of the projection neurons by applying a GABA receptor blocker to the area. However, injections of the GABA(A) receptor blocker bicuculline or the GABA(B) receptor blocker saclofen did not significantly affect food intake. Thus, it appears that the expression of the feeding response depends on an NMDA-preferring receptor-mediated activation of LH neurons and is not the result of disinhibiting LH cells by disrupting transmission at GABA synapses.