The GABAB 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

Psychopharmacology
Rick Shin, Satoshi Ikemoto

Abstract

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

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Citations

May 15, 2013·Neuropharmacology·Satoshi Ikemoto, Antonello Bonci
Jan 28, 2016·Neuroscience and Biobehavioral Reviews·Chelcie F Heaney, Jefferson W Kinney
Feb 26, 2015·ELife·Jeremiah Y CohenNaoshige Uchida
Nov 30, 2019·Science·Satoshi Ikemoto
Dec 25, 2013·Journal of Clinical Psychopharmacology·Konstantinos MargetisDamianos Sakas
Jul 10, 2020·Annual Review of Neuroscience·Zhixiang LiuMinmin Luo

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