ACTIVATION OF VENTRAL TEGMENTAL GABA(B) RECEPTORS INHIBITS MORPHINE-INDUCED PLACE PREFERENCE IN RATS

The effect of microinjection of a GABA(B) receptor agonist, baclofen, into the ventral tegmental area on the rewarding effect of morphine wa s investigated using the conditioned place preference paradigm in rats . Morphine (1-8 mg/kg, s.c.) caused a dose-related place preference fo r the drug-associated place. In contrast, microinjection of baclofen ( 0.1-1 nmol/side) into the ventral tegmental area did not produce a sig nificant preference for either compartment of the test box. Pretreatme nt with baclofen (0.1-1 nmol/side) into the ventral tegmental area dos e dependently suppressed the morphine (8 mg/kg, s.c.)-induced place pr eference. This suppression of the morphine (8 mg/kg, s.c.)-induced pla ce preference by baclofen (1 nmol/side) was reversed by treatment of t he ventral tegmental area with the GABA(B) receptor antagonist, 2-hydr oxysaclofen (1 nmol/side), but not with the GABA(A) receptor antagonis t bicuculline (1 nmol/side), The present results suggest that a decrea se in GABA(B) neurotransmission in the ventral tegmental area, which m ay be produced via inhibition of a tonic GABAergic input by morphine, may be involved in the expression of the rewarding effect of morphine.