Chronic exposure to morphine does not alter the neural tissues subserving its acute rewarding properties: apparent tolerance is overshadowing.
Drug-naive, but not morphine-dependent, rats preferred places paired with morphine (2 mg/kg) over unfamiliar neutral places. Both drug-naive and morphine-dependent rats preferred places paired with higher doses of morphine (20 mg/kg) over unfamiliar places. Lesions of the tegmental pedunculopontine nucleus (TPP) blocked the conditioned place preferences produced by both 2 and 20 mg/kg morphine in drug-naive rats but not the preferences produced by 20 mg/kg morphine in dependent rats. When morphine-dependent animals received withdrawal-alleviating doses of morphine (20 mg/kg) 3.5 hr before pairing one environment with 2 mg/kg morphine, they showed morphine-conditioned place preferences that were abolished by TPP lesions. The apparent behavioral tolerance to the TPP-mediated rewarding effects may have resulted from overshadowing by separate withdrawal-related motivational mechanisms.
Bechara
A
A
Department of Anatomy, University of Toronto, Ontario, Canada.
van der Kooy
D
D
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001245:Association Learning / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D011149:Pons / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D012931:Social Environment; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects*
D011957:Receptors, Opioid; D009020:Morphine