A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism.
Repeated exposure to drugs of abuse produces forms of experience-dependent plasticity including behavioral sensitization. Although a single exposure to many addicting substances elicits locomotor sensitization, there is little information regarding the motivational effects of such single exposures. This study demonstrates that a single cocaine exposure enhances both rewarding and aversive forms of opioid place conditioning. Rats were given a single injection of cocaine (15 mg/kg i.p.) in their home cage at different times before conditioning. This treatment enhanced conditioned place preference (CPP) to morphine (2 x 10 mg/kg s.c.) if training began 1 or 5 but not 10 days after the cocaine injection. A single cocaine exposure also enhanced conditioned place aversion (CPA) to the kappa-opioid receptor agonist U69593 (2 x 0.16 mg/kg s.c.). Compared to morphine CPP, U69593 CPA was delayed and persistent. It was not observed at 1 day but appeared if the conditioning began 5 or 10 days after the cocaine injection. Although the cocaine-induced enhancements of both morphine CPP and U69593 CPA followed different time courses, suggesting different mechanisms, both effects were blocked by injection of the N-methyl-d-aspartate receptor antagonist MK-801 (0.5 nmol bilaterally) into the ventral tegmental area, immediately before the cocaine injection. Thus, through a circuit involving the ventral tegmental area, a single cocaine exposure enhanced both micro-opioid receptor reward and kappa-opioid receptor aversion.
Kim
Joseph A
JA
Ernest Gallo Clinic and Research Center, Wheeler Center for the Neurobiology of Addiction and Department of Neurology, University of California, San Francisco, CA 94143, USA.
Pollak
Kelly A
KA
Hjelmstad
Gregory O
GO
Fields
Howard L
HL
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology*
D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D018691:Excitatory Amino Acid Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D016291:Dizocilpine Maleate; D009020:Morphine; D003042:Cocaine; C045444:U 69593