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.
BACKGROUND
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.


OBJECTIVE
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.


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 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.


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 GABAB receptors are involved in tonic inhibitory control over reward processes.
Shin
Rick
R
Behavioral Neuroscience Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA.
Ikemoto
Satoshi
S
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D058786:GABA-B Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009025:Morpholines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012646:Self Administration
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D001552:Benzazepines; D058786:GABA-B Receptor Agonists; D009025:Morpholines; C534628:SCH 23390; D001418:Baclofen