Effect of adenosine receptor agonists and antagonists on the expression of opiate withdrawal in rats.
The effects of the selective A1 adenosine receptor agonist N6-cyclopentyladenosine (CPA) and the selective A2a agonist 2-[p-(2-carboxethyl)phenylethyl-ethylamino]-5'-ethylcarboxamidoade nosine (CGS 21680) (each at 0.03, 0.1 and 0.3 mg/kg, SC) as well as the selective A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), non-selective antagonists 3-isobutyl-1-methylxanthine (IBMX), aminophylline, 3,7-dimethyl-1-propargyl-xanthine (DMPX) and 8(p-sulfophenyl)-theophylline (8-SPT) were investigated (each at 5, 10 and 30 mg/kg, SC) for their ability to alter the naloxone-precipitated opiate withdrawal syndrome in morphine-dependent rats. Effects of CPA and CGS 21680 on opiate withdrawal in the presence of aminophylline were also investigated. Both 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 amount of faecal matter produced. The incidence of body shakes was significantly increased by DMPX, 8-SPT and IBMX. Neither CPA nor CGS 21680 were able to reverse the significant increase in the incidence of jumps caused by aminophylline. These data suggest that there is a role for endogenous adenosine in the modulation of the opiate abstinence syndrome and both A1 and A2a adenosine receptors are involved in this phenomenon.
Salem
A
A
School of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Hope
W
W
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003672:Defecation / Q000187:drug effects; D005260:Female; D009020:Morphine / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D009292:Narcotic Antagonists; D009294:Narcotics; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D009270:Naloxone; D009020:Morphine