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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.
Psychopharmacology (Berl) 2005; 179(4):804-12P

Abstract

RATIONALE

Many behavioral effects of delta-9-tetrahydrocannabinol (THC), including its discriminative-stimulus effects, are modulated by endogenous opioid systems.

OBJECTIVE

To investigate opioid receptor subtypes involved in the discriminative effects of THC.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, Division of Intramural Research, National Institute of Health, Room 318, 5500 Nathan Shock Drive, Baltimore, MD, 21224, USA. msolinas@intra.nida.nih.govNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15619107

Citation

Solinas, Marcello, and Steven R. Goldberg. "Involvement of Mu-, Delta- and Kappa-opioid Receptor Subtypes in the Discriminative-stimulus Effects of Delta-9-tetrahydrocannabinol (THC) in Rats." Psychopharmacology, vol. 179, no. 4, 2005, pp. 804-12.
Solinas M, Goldberg SR. Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats. Psychopharmacology (Berl). 2005;179(4):804-12.
Solinas, M., & Goldberg, S. R. (2005). Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats. Psychopharmacology, 179(4), pp. 804-12.
Solinas M, Goldberg SR. Involvement of Mu-, Delta- and Kappa-opioid Receptor Subtypes in the Discriminative-stimulus Effects of Delta-9-tetrahydrocannabinol (THC) in Rats. Psychopharmacology (Berl). 2005;179(4):804-12. PubMed PMID: 15619107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats. AU - Solinas,Marcello, AU - Goldberg,Steven R, Y1 - 2004/12/24/ PY - 2004/07/30/received PY - 2004/11/02/accepted PY - 2004/12/25/pubmed PY - 2005/9/16/medline PY - 2004/12/25/entrez SP - 804 EP - 12 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 179 IS - 4 N2 - RATIONALE: Many behavioral effects of delta-9-tetrahydrocannabinol (THC), including its discriminative-stimulus effects, are modulated by endogenous opioid systems. OBJECTIVE: To investigate opioid receptor subtypes involved in the discriminative effects of THC. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/15619107/Involvement_of_mu__delta__and_kappa_opioid_receptor_subtypes_in_the_discriminative_stimulus_effects_of_delta_9_tetrahydrocannabinol__THC__in_rats_ L2 - https://dx.doi.org/10.1007/s00213-004-2118-x DB - PRIME DP - Unbound Medicine ER -