Multiple opiate receptors may be involved in suppressing γ-aminobutyrate release in substantia nigra

Abstract

Slices of rat substantia nigra were preloaded with tritiated γ-aminobutyrate (GABA) or dopamine (DA) and perfused with Krebs solution containing 5 μM aminooxyacetic acid or 10 μM nialamide to inhibit the catabolism of GABA and DA respectively. Repeated brief exposures to high potassium medium (+ 30 mM K + for 1 min) evoked a consistent pattern of calcium-dependent 3H efflux against which the effects of opiates (10–400 μM) were assessed. Opiate agonists inhibited K +-induced 3H-GABA efflux in the following decreasing order of potency : bremazocine > D-Ala 2-Met 5 -enkephalinamide (ENK) > SKF 10047 ⪢ morphine, consistent with the participation of κ,δ,σ and to a lesser extent μ opiate receptors respectively. Naloxone (1 μM) partially antagonised the response to morphine and ENK, while ICI 154129 attenuated ENK only. Save for a GABA-releasing action of SKF 10047 at high doses, none of the compounds altered basal outflow of 3H-GABA. Naloxone, in the dose range 10–400 μM, also significantly inhibited depolarisation-induced release of 3H-GABA. In parallel experiments none of the compounds tested were found to influence 3H-DA release in concentrations up to 40 μM, but thereafter suppressed K +-induced 3H-DA outflow indiscriminately. The results are discussed with reference to the possible mechanism(s) via which injected and endogenous opiates may affect motor performance by attenuating GABA transmission in the nigra.