An analysis of GABA receptor changes in the discrete regions of mouse brain after acute and chronic treatments with morphine

Abstract: The effects of morphine on the affinity and distribution of GABA receptors in the mouse regions (striatum, medulla, diencephalon, cortex, and cerebellum) were investigated in relation to: (a) acute administration, (b) chronic administration (tolerance), (c) precipitated withdrawal by naloxone, an opiate antagonist, and (d) abrupt withdrawal for 8 and 24 h. The alterations in the affinity as reflected by the dissociation constant (K_D) and the number of receptors (B_max) in the synaptic membranes obtained from controls and various treatments were determined by radioligand binding assay using ³H]muscimol as a ligand. Significant changes were observed in striatum, medulla, and diencephalon, whereas other regions including whole brain exhibited marginal changes. In general the number of GABA receptors increased after tolerance development, which upon abrupt withdrawal returned to control levels except in the case of naloxone-induced precipitated withdrawal. The affinity changes in different regions were diverse in nature and were not evident in the whole brain membranes. These results indicate that: (a) the regional alterations in the affinity and distribution of GABA receptors may play a role in the induction, maintenance, and regression of morphine tolerance; (b) abrupt withdrawal and antagonist precipitated withdrawal affect the GABA system differently, (c) chronic morphine treatment appears to influence the GABA receptors in the cerebellum, a region generally known for its lack of opiate receptors.