RETRACTED: Bidirectional dopaminergic modulation of excitatory synaptic transmission in orexin neurons (Retracted article. See vol. 32, pg. 9116, 2012)

Orexin neurons in the lateral hypothalamus (LH)/perifornical area (PFA) are known to promote food intake as well as provide excitatory influence on the dopaminergic reward pathway. Dopamine (DA), in turn, inhibits the reward pathway and food intake through its action in the LH/PFA. However, the cellular mechanism by which DA modulates orexin neurons remains largely unknown. Therefore, we examined the effect of DA on the excitatory neurotransmission to orexin neurons. Whole-cell patch-clamp recordings were performed using acute rat hypothalamic slices, and orexin neurons were identified by their electrophysiological and immunohistochemical characteristics. Pharmacologically isolated action potential-independent miniatures EPSCs (mEPSCs) were monitored. Bath application of DA induced a bidirectional effect on the excitatory synaptic transmission dose dependently. A low dose of DA (1 mu M) increased mEPSC frequency, which was blocked by the D-1-like receptor antagonist SCH 23390, and mimicked by the D-1-like receptor agonist SKF 81297. In contrast, higher doses of DA (10-100 mu M) decreased mEPSC frequency, which could be blocked with the D-2-like receptor antagonist, sulpiride. Quinpirole, the D-2-like receptor agonist, also reduced mEPSC frequency. None of these compounds affected the mEPSCs amplitude, suggesting the locus of action was presynaptic. Furthermore, DA (1 mu M) induced an increase in the action potential firing, whereas DA (100 mu M) hyperpolarized and ceased the firing of orexin neurons, indicating the effect of DA on excitatory synaptic transmission may influence the activity of the postsynaptic cell. In conclusion, our results suggest that D-1- and D-2- like receptors have opposing effects on the excitatory presynaptic terminals impinging onto orexin neurons.