Activation of ventral tegmental GABAB receptors inhibits morphine-induced place preference in rats.
The effect of microinjection of a GABAB receptor agonist, baclofen, into the ventral tegmental area on the rewarding effect of morphine was investigated using the conditioned place preference paradigm in rats. Morphine (1-8 mg/kg, s.c.) caused a dose-related place preference for the drug-associated place. In contrast, microinjection of baclofen (0.1-1 nmol/side) into the ventral tegmental area did not produce a significant preference for either compartment of the test box. Pretreatment with baclofen (0.1-1 nmol/side) into the ventral tegmental area dose dependently suppressed the morphine (8 mg/kg, s.c)-induced place preference. This suppression of the morphine (8 mg/kg, s.c.)-induced place preference by baclofen (1 nmol/side), but not with the GABAA receptor antagonist bicuculline (1 nmol/side). The present results suggest that a decrease in GABAB neurotransmission in the ventral tegmental area, which may be produced via inhibition of a tonic GABAergic input by morphine, may be involved in the expression of the rewarding effect of morphine.
Tsuji
M
M
Tsukuba Research Laboratories, Experimental Biomedical Research Inc. (Jisseiken), Ibaraki, Japan.
Nakagawa
Y
Y
Ishibashi
Y
Y
Yoshii
T
T
Takashima
T
T
Shimada
M
M
Suzuki
T
T
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000502:physiology* / Q000648:ultrastructure*
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D009292:Narcotic Antagonists; D009294:Narcotics; D009020:Morphine; D001418:Baclofen