MUTUAL INTERACTION BETWEEN PRESYNAPTIC ALPHA-2-ADRENOCEPTORS AND OPIOID KAPPA-RECEPTORS AT THE NORADRENERGIC AXONS OF RABBIT BRAIN CORTEX

The interaction between presynaptic, release-inhibiting .alpha.2-adrenoceptors and opioid receptors was studied in slices of the parieto-occiptal cortex of rabbits. The slices were preincubated with 3H-noradrenaline and then superfused with 3H-noradrenaline-free medium and stimulated electrically (3 or 7 Hz, 2 or 4 V/cm voltage drop between the electrodes). Clonidine and ethylketocyclazocine (EK) depressed, whereas yohimbine increased the electrically evoked overflow of tritium. When clonidine was administered first and retained in the medium for the rest of the experiment, the overflow-inhibiting effect of EK was reduced. When yohimbine was administered first and kept for the rest of the experiment, the effect of EK was enhanced. When, finally, EK was administered first and clonidine as the second drug, the overflow-inhibiting effect of clonidine was attenuated. The changes in the effect of EK (by clonidine or yohimbine) and clonidine (by EK) were not due to the changes in release per se produced by the drugs that were given first. Naloxone shifted the concentration-response curve of EK to the right; the dissociation constant of the naloxone-receptor complex, calculated from the shift, was 13 nmol/l. It is concluded that there is an interaction between presynaptic .alpha.2-adrenoceptors and opioid .kappa.-receptors, either at the level of the receptors themselves or of the post-receptor reaction chains. Activation of one kind of receptor blunts the inhibition of release produced by activation of the other kind of receptor.