The effects of adenosine receptor agonists and antagonists on morphine state-dependent memory of passive avoidance.
Pretraining administration of morphine (5 mg/kg, intraperitonically) in a step-down passive avoidance task led to state-dependent learning with impaired retrieval on the test day that was dose-dependently restored by pretest administration of morphine (0.5, 1, 3, and 5 mg/kg). This restoration was reversible by pretest naloxone administration. Pretest administration of adenosine receptor antagonists theophylline or 8-phenyltheophylline (8-PT) did not alter morphine-induced amnesia. However, both the antagonists inhibited the restoration of memory by pretest morphine (5 mg/kg). Adenosine A(1) receptor agonists N(6)-cyclohexyladenosine (CHA) or N(6)-phenylisopropyladenosine (R-PIA) only at the higher doses used, and adenosine A(2) receptor agonist 5'-N-ethylcarboxaminoadenosine (NECA), at all doses used, decreased morphine-induced amnesia in a dose-dependent manner. Pretest administration of low doses of CHA, R-PIA, or NECA significantly showed additive effects with low dose pretest morphine (1 mg/kg) in restoring memory. The promnestic effects of high-dose CHA and R-PIA were inhibited by theophylline or 8-PT but not by naloxone. The additive effects of low-dose CHA or R-PIA and morphine were inhibited by theophylline, 8-PT, or a higher dose of naloxone. The promnestic effect of NECA and its additive effect with low-dose morphine were both inhibited by theophylline and naloxone but not by 8-PT. It is concluded that activation of the adenosinergic system, through both A(1) and A(2) receptors, can reverse morphine-induced amnesia and is involved in morphine state of memory.
Khavandgar
Simin
S
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Homayoun
Houman
H
Torkaman-Boutorabi
Anahita
A
Zarrindast
Mohammad Reza
MR
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000701:Analgesics, Opioid; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; C047235:N-(1-methyl-2-phenylethyl)adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C048599:N(6)-cyclopentyladenosine; D009020:Morphine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine