EFFECT OF ADENOSINE RECEPTOR AGONISTS AND ANTAGONISTS ON THE EXPRESSION OF OPIATE WITHDRAWAL IN RATS

The effects of the selective A(1) adenosine receptor agonist N-6-cyclo pentyladenosine (CPA) and the selective A(2a) agonist arboxethyl)pheny lethyl-ethylamino]-5'-ethylcarboxa midoadenosine (CGS 21680) (each at 0.03, 0.1 and 0.3 mg/kg, SC) as well as the selective A(1) adenosine r eceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), non-sel ective antagonists 3-isobutyl-1-methylxanthine (IBMX), aminophylline, 3,7-dimethyl-1-propargyl-xanthine (DMPX) and 8(p-sulfophenyl)-theophyl line (8-SPT) were investigated (each at 5, 10 and 30 mg/kg, SC) for th eir ability to alter the naloxone-precipitated opiate withdrawal syndr ome in morphine-dependent rats. Effects of CPA and CGS 21680 on opiate withdrawal in the presence of aminophylline were also investigated. B oth CPA and CGS 21680, caused a significant reduction in the incidence of body shakes, teeth chatter and paw shakes and decreased the amount of faecal matter produced. DPCPX, IBMX, DMPX, 8-SPT and aminophylline significantly increased the incidence of jumps and decreased the amou nt of faecal matter produced. The incidence of body shakes was signifi cantly increased by DMPX, 8-SPT and IBMX. Neither CPA nor CGS 21680 we re able to reverse the significant increase in the incidence of jumps caused by aminophylline. These data suggest that there is a role for e ndogenous adenosine in the modulation of the opiate abstinence syndrom e and both A(1) and A(2a) adenosine receptors are involved in this phe nomenon. (C) 1997 Elsevier Science Inc.