Effects of GABAB receptor blockade on lateral habenula glutamatergic neuron activity following morphine injection in the rat: an electrophysiological study.

Abstract

Background and purpose: The lateral habenula (LHb), a key area in the regulation of the reward system, exerts a major influence on midbrain neurons. It has been shown that the gamma-aminobutyric acid (GABA)- ergic system plays the main role in morphine dependency. The role of GABA type B receptors (GABA_BR_s) in the regulation of LHb neural activity in response to morphine, remains unknown. In this study, the effect of GABA_BR_s blockade in response to morphine was assessed on the neuronal activity in the LHb.

Experimental approach: The baseline firing rate was recorded for 15 min, then morphine (5 mg/kg; s.c) and phaclofen (0, 0.5, 1, and 2 μg/rat), a GABA_BR_s' antagonist, were microinjected into the LHb. Their effects on firing LHb neurons were investigated using an extracellular single-unit recording in male rats.

Findings/results: The results revealed that morphine decreased neuronal activity, and GABA_BR_s blockade alone did not have any effect on the neuronal activity of the LHb. A low dose of the antagonist had no significant effect on neuronal firing rate, while blockade with doses of 1 and 2 μg/rat of the antagonist could significantly prevent the inhibitory effects of morphine on the LHb neuronal activity.

Conclusion and implications: This result indicated that GABA_BR_s have a potential modulator effect, in response to morphine in the LHb.