Lateral habenula electrical stimulation with different intensities in combination with GABA_B receptor antagonist...

The lateral habenula (LHb) plays a principal role in response to aversive stimuli and negative emotional states. In this study, we have evaluated the effects of unilateral electrical stimulation (e-stim) of the LHb on morphine-conditioned place preference (CPP), before or after bilateral injections of Gamma-aminobutyric acid-B receptor (GABA_BR) antagonist, phaclofen, in male rats. Morphine (5 mg/kg; s.c.) induced a significant CPP, using a 5-day CPP paradigm. Intra-LHb microinjection of phaclofen or the LHb e-stim decreased only the acquisition of CPP. The 150 μA stimulation plus phaclofen significantly suppressed the expression phase but induced aversion in the acquisition of CPP, and an e-stim of 25 μA in combination with the antagonist, significantly prevented only the acquisition phase. The findings of this study confirm the possible role of GABA_BRs in the LHb on the acquisition and the expression of CPP. These results show that e-stim of LHb alone or plus phaclofen may change the GABA transmission, involving into CPP. Therefore, the GABAergic system, especially through GABA_BRs, may play a prominent role in the behavioral responses to morphine-induced CPP by LHb stimulation.