MU-OPIOID PEPTIDES INHIBIT THALAMIC NEURONS

Opioidergic inhibition of neurons in the centrolateral nucleus of the thalamus was investigated using an in vitro thalamic slice preparation from young rats. The mu-opioid receptor agonist D-Ala(2),N-Me-Phe(4), glycinol 5-enkephalin (DAMGO) evoked a hyperpolarization and decrease in input resistance that was reversible, concentration-dependent, and persisted in the presence of tetrodotoxin. Application of the specific mu-receptor antagonist Cys(2),Tyr(3),Om(5),Pen(7)-amide blocked this response. The respective 6- and kappa-opioid receptor agonists, (D-Pen (2),D-Pen(5))-enkephalin and (+/-)-trans-U-50488 methanesulfonate had no effect. Voltage-clamp experiments showed that DAMGO activated an in wardly rectifying potassium conductance (GK(IR)) characterized by rect ification at hyperpolarized potentials that increased in elevated extr acellular potassium concentrations, a complete block by Ba2+ (1 mM), a nd a voltage-dependent block by Cs+. The extent of mu-opioid inhibitio n in other thalamic nuclei was then investigated. Widespread inhibitio n similar to that seen in the centrolateral nucleus was observed in a number of sensory, motor, intralaminar, and midline nuclei. Our result s suggest that the net action of opioids would depend on their source: exogenous (systemically administered) opiates inhibiting the entire t halamus and favoring the shift of cell firing from tonic to bursting m ode; and endogenously released opioids acting on specific thalamic nuc lei, their release depending on the origin of the presynaptic input.