THE EFFECT OF GABAB RECEPTOR ACTIVATION WITHIN THE VENTRAL TEGMENTAL AREA ON MORPHINE-INDUCED INCENTIVE SENSITIZATION IN FEMALE RATS

Abstract

Repeated administration of morphine sensitizes animals to the stimulant and rewarding properties of the drug. It may also alter the expression and function of GABA receptors within the ventral tegmental area (VTA), a midbrain region that is implicated in morphine action. In the present study, the effect of activation of GABAB receptor subtypes within the VTA on morphine-induced incentive sensitization in female Wistar rats (250-300 g) was investigated. Female rats (n = 8) were chronically implanted with a 21-gauge cannula in the VTA (V = 8.5, L = 0.9, and A = -4.8 mm from bregma). One week after the surgery, the animals received morphine (5 mg/kg, s.c.) in their home cage for three consecutive days. Five days later, the animals were conditioned with an ineffective dose of morphine in a two compartment un-biased apparatus. Different doses of GABAB receptor agonist, baclofen (1.5, 6, and 12 ng/rat) were administered to the animals 5 min before the test. The results indicated that morphine administration to the animals in three consecutive days produces sensitization in which low doses of morphine (0.5 mg/kg, s.c.) induced CPP. Furthermore, administration of low doses of baclofen (1.5 and 6 ng/rat, i.VTA) enhanced, while higher doses of baclofen (12 ng/rat, i.VTA) reduced the morphine effects. The results indicated that activation of GABAB receptors within the VTA in morphine-sensitized animals produces a biphasic response, which may be due to pre and post GABAB receptor activation.