The GABA_B receptor agonist baclofen administered into the median and dorsal raphe nuclei is rewarding as shown by intracranial self-administration and conditioned place preference in rats

Abstract

Rationale

The midbrain raphe regions have long been implicated in affective processes and disorders. There is increasing evidence to suggest that the median (MR) and dorsal raphe nuclei (DR) tonically inhibit reward-related processes.

Objectives

Stimulation of GABA_B receptors in the midbrain raphe nuclei is known to inhibit local neurons, especially serotonergic neurons. We sought to determine if injections of the GABA_B receptor agonist baclofen into the MR or DR are rewarding, using intracranial self-administration and conditioned place preference.

Results

Rats quickly learned to lever press for infusions of baclofen (0.1–2.5 mM) into the MR, but not the ventral tegmental area or central linear nucleus. Rats increased lever pressing associated with intra-DR baclofen infusions, but not readily. Baclofen self-administration into the MR or DR was attenuated by coadministration of the GABA_B receptor antagonist SCH 50911 (1 mM) or systemic pretreatment with the dopamine receptor antagonist SCH 23390 (0.025 mg/kg, i.p.). In addition, intra-DR and intra-MR injections of baclofen induced conditioned place preference; injection into DR was more effective.

Conclusions

Baclofen injections into the midbrain raphe nuclei are rewarding. Baclofen was more readily self-administered into the MR than into the DR, while baclofen injections into the DR more readily induced conditioned place preference than those into the MR. These sites may be differentially involved in aspects of reward. These findings suggest that MR or DR neurons containing GABA_B receptors are involved in tonic inhibitory control over reward processes.