A single exposure to morphine induces long-lasting behavioural and neurochemical sensitization in rats.
Repeated exposure to drugs of abuse causes persistent behavioural sensitization and associated adaptations in striatal neurotransmission, which is thought to play an important role in certain aspects of drug addiction. Remarkably, even a single exposure to psychostimulant drugs such as amphetamine or cocaine can be sufficient to elicit long-lasting sensitization. The present study was designed to evaluate whether long-lasting behavioural and neurochemical sensitization can also be evoked by a single exposure to morphine, an opiate drug of abuse. Rats were pretreated once with morphine (2, 10 or 30 mg/kg). Three weeks later, the locomotor effects of morphine and amphetamine, as well as the electrically evoked release of [3H]dopamine and [14C]acetylcholine from slices of nucleus accumbens and caudate-putamen, was assessed. In morphine-pretreated rats, the psychomotor effects of morphine and amphetamine were sensitized. In addition, the electrically evoked release of [3H]dopamine and [14C]acetylcholine was augmented in slices of nucleus accumbens and caudate-putamen from morphine-pretreated animals. Although the sensitization of the locomotor effect of morphine was less profound than previously observed after repeated intermittent morphine treatment, the enduring behavioural and neurochemical consequences of a single and repeated intermittent morphine treatment appear to be highly comparable. We therefore conclude that a single exposure to morphine induces long-lasting behavioural sensitization and associated neuroadaptations.
Vanderschuren
L J
LJ
Drug Abuse Program, Research Institute Neurosciences Vrije Universiteit, Department of Medical Pharmacology, VU Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. ljmj.vanderschuren.pharm@med.vu.nl
De Vries
T J
TJ
Wardeh
G
G
Hogenboom
F A
FA
Schoffelmeer
A N
AN
D000109:Acetylcholine / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium / Q000378:metabolism
D018377:Neurotransmitter Agents; D014316:Tritium; D009020:Morphine; D000661:Amphetamine; D000109:Acetylcholine; D004298:Dopamine