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Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats.

Marcello Solinas, Steven R Goldberg

Psychopharmacology June 2005 DOI: 10.1007/s00213-004-2118-x (opens in new tab)

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AI-extracted from the abstract
Characteristics Drug-discrimination study in rats Peer reviewed
Population Rats trained to discriminate 3 mg/kg i.p. THC from vehicle
Interventions delta-9-tetrahydrocannabinol (THC) heroin SNC-80 U50488 naltrexone naltrindole
Dose THC 3 mg/kg i.p.; heroin 0.3-1.0 mg/kg i.p.; SNC-80 1-10 mg/kg i.p.; U50488 1-10 mg/kg i.p.; naltrexone 0.1-1 mg/kg i.p.; naltrindole 1-10 mg/kg i.p.; nor-binaltorphimine 5 mg/kg s.c.
Topics Cannabis
Key points The mu-opioid receptor appears to be involved in the discriminative-stimulus effects of THC, whereas delta- and kappa-opioid receptors do not. Heroin shifted the THC dose-response curve leftward and naltrexone shifted it rightward and blocked heroin's effect, while SNC-80, U50488, naltrindole, and nor-binaltorphimine did not. The authors suggest that THC's discriminative and rewarding effects may share similar neural mechanisms.

Abstract

Many behavioral effects of delta-9-tetrahydrocannabinol (THC), including its discriminative-stimulus effects, are modulated by endogenous opioid systems. To investigate opioid receptor subtypes involved in the discriminative effects of THC. Rats trained to discriminate 3 mg/kg i.p. of THC from vehicle using a two-lever operant drug-discrimination procedure, were tested with compounds that bind preferentially or selectively to either mu-, delta- or kappa-opioid receptors. The preferential mu-opioid receptor agonist heroin (0.3-1.0 mg/kg, i.p.), the selective delta-opioid receptor agonist SNC-80 (1-10 mg/kg, i.p.) and the selective kappa-opioid receptor agonist U50488 (1-10 mg/kg, i.p.) did not produce generalization to the discriminative effects of THC when given alone. However, heroin, but not SNC-80 or U50488, significantly shifted the dose-response curve for THC discrimination to the left. Also, the preferential mu-opioid receptor antagonist naltrexone (0.1-1 mg/kg, i.p.), the selective delta-opioid receptor antagonist, naltrindole (1-10 mg/kg, i.p.) and the kappa-opioid receptor antagonist nor-binaltorphimine (n-BNI, 5 mg/kg, s.c.), did not significantly reduce the discriminative effects of the training dose of THC. However, naltrexone, but not naltrindole or n-BNI, significantly shifted the dose-response curve for THC discrimination to the right. Finally, naltrexone, but not naltrindole or n-BNI, blocked the leftward shift in the dose-response curve for THC discrimination produced by heroin. mu- but not delta- or kappa-opioid receptors are involved in the discriminative effects of THC. Given the role that mu-opioid receptors play in THC's rewarding effects, the present findings suggest that discriminative-stimulus effects and rewarding effects of THC involve similar neural mechanisms.

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