GAMMA-VINYL-GABA POTENTIATES THE SEVERITY OF NALOXONE-PRECIPITATED ABSTINENCE SIGNS IN MORPHINE-DEPENDENT RATS

Effects of gamma-vinyl-GABA (GVG), an antiepileptic drug that inhibits GABA transaminase and increases extracellular GABA concentrations in the brain, were investigated on the morphine abstinence syndrome (AS) in male Wistar rats. Two morphine pellets (75 mg morphine base in each ) were implanted subcutaneously on the back of the rats. Seventy-two h ours after the morphine implantation, naloxone (NL, 2 mg kg(-1)) was i njected intraperitoneally (i.p.) to induce precipitated morphine AS. G VG was administered at the doses of 250 mg kg(-1) (n = 11) and 500 mg kg(-1) (n = 11) i.p. 24 h prior to AS and at the dose of 500 mg kg(-1) (n = 13) i.p. 6 h prior to AS. Immediately after NL injections, rats were observed for 5 min and AS signs (jumping, teeth chattering, wet d og shake, diarrhoea, ptosis and defecation) were assessed. The behavio ural signs of GVG-treated rats were compared with the control groups ( n = 10) during the AS. Jumping, wet dog shake, teeth chattering were f ound to be significantly increased in all of the GVG-treated groups. P tosis was found to have increased in only 500 mg kg(-1) GVG groups. GV G potentiated the severity of morphine AS signs. GVG does not seem to have any therapeutic potential for treatment of morphine abstinence un like some other drugs that enhance GABAergic transmission. (C) 1998 Th e Italian Pharmacological Society.