Gamma-vinyl-GABA potentiates the severity of naloxone-precipitated abstinence signs in morphine-dependent rats

Abstract

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 hours after the morphine implantation, naloxone (NL, 2 mg kg(-1)) was injected intraperitoneally (i.p.) to induce precipitated morphine AS. GVG 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 dog shake, diarrhoea, ptosis and defecation) were assessed. The behavioural signs of GVG-treated rats were compared with the control groups (n = 10) during the AS. Jumping, wet dog shake, teeth chattering were found to be significantly increased in all of the GVG-treated groups. Ptosis was found to have increased in only 500 mg kg(-1) GVG groups. GVG potentiated the severity of morphine AS signs. GVG does not seem to have any therapeutic potential for treatment of morphine abstinence unlike some other drugs that enhance GABAergic transmission. (C) 1998 The Italian Pharmacological Society.