Opioid inhibition of spontaneously active neurons of the rat arcuate nucleus in vitro.
The effects of opioid agonists were determined on single-unit activity recorded from the arcuate nucleus (ARC) in perfused, coronal slices of hypothalamus taken from proestrous rats. The selective, mu-receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) produced a concentration-dependent decrease in the firing rate of 70-78% of the units tested. The concentration of DAGO that induced maximal inhibition of firing was approximately 0.5 microM. This inhibition of firing frequency occurred irrespective of cell location, firing pattern or baseline firing frequency. The effect of DAGO was antagonized by the opioid antagonist naloxone (0.1 microM). The selective, kappa-receptor agonist, trans-(+)-3,4 dichloro-N-methyl-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methane sulfonate (U50,488H) did not decrease the firing rate in cells which did respond to DAGO. Blockade of synaptic activity decreased the level of spontaneous activity but did not prevent the inhibitory action of DAGO. These data support the hypothesis that opioids, through activation of mu-receptors, inhibit neuronal activity in the arcuate nucleus. Furthermore, the opioid inhibition occurs, in part, via a direct postsynaptic action.
Loose
M D
MD
Department of Physiology, Oregon Health Sciences University, Portland 97201.
Kelly
M J
MJ
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer