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Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study.
Brain Res. 1993 Jul 09; 616(1-2):293-302.BR

Abstract

The active ingredient of marijuana is (-)-delta 9-tetrahydrocannabinol (delta 9-THC). delta 9-THC and other natural and synthetic cannabinoids such as CP-55,940 inhibit spontaneous activity and produce catalepsy in animals in a receptor-mediated fashion. Tolerance develops to the motor effects of delta 9-THC after repeated administration. To test the hypothesis that tolerance is mediated by changes in cannabinoid receptor binding characteristics, we used quantitative in vitro autoradiography of [3H]CP-55,940 binding to striatal brain sections from rats treated either chronically or acutely with delta 9-THC, CP-55,940, or the inactive natural cannabinoid cannabidiol. In the chronic conditions, rats were given daily i.p. injections of delta 9-THC (10 mg/kg), cannabidiol (10 mg/kg), or CP-55,940 (1, 3, or 10 mg/kg) for 2 weeks and sacrificed 30 min after the last injection. In the acute condition, animals received a single dose (10 mg/kg) prior to sacrifice. Rats developed tolerance to the inhibitory effects of delta 9-THC and CP-55,940, assayed in an open field on days 1, 7, and 14. Cannabidiol had no effect on behavior. Densitometry of [3H]CP-55,940 binding to brain sections showed that delta 9-THC- and CP-55,940-treated animals had homogeneous decreases in binding in all structures measured at the selected striatal levels. Cannabidiol had no effect on binding. Analysis of binding parameters showed that alterations in the acute condition were attributed to changes in affinity (KD), whereas the major changes in the chronic condition were attributed to a lowering of capacity (Bmax). The effects in the 1, 3, and 10 mg/kg CP-55,940 conditions were dose-dependent and paralleled the behavioral data showing that the animals given the highest dose developed the greatest degree of tolerance. The data suggest that tolerance to cannabinoids results at least in part from agonist-induced receptor down-regulation.

Authors+Show Affiliations

Section on Functional Neuroanatomy, NIMH Bethesda, MD 20892.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8395305

Citation

Oviedo, A, et al. "Chronic Cannabinoid Administration Alters Cannabinoid Receptor Binding in Rat Brain: a Quantitative Autoradiographic Study." Brain Research, vol. 616, no. 1-2, 1993, pp. 293-302.
Oviedo A, Glowa J, Herkenham M. Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study. Brain Res. 1993;616(1-2):293-302.
Oviedo, A., Glowa, J., & Herkenham, M. (1993). Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study. Brain Research, 616(1-2), 293-302.
Oviedo A, Glowa J, Herkenham M. Chronic Cannabinoid Administration Alters Cannabinoid Receptor Binding in Rat Brain: a Quantitative Autoradiographic Study. Brain Res. 1993 Jul 9;616(1-2):293-302. PubMed PMID: 8395305.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study. AU - Oviedo,A, AU - Glowa,J, AU - Herkenham,M, PY - 1993/7/9/pubmed PY - 1993/7/9/medline PY - 1993/7/9/entrez SP - 293 EP - 302 JF - Brain research JO - Brain Res VL - 616 IS - 1-2 N2 - The active ingredient of marijuana is (-)-delta 9-tetrahydrocannabinol (delta 9-THC). delta 9-THC and other natural and synthetic cannabinoids such as CP-55,940 inhibit spontaneous activity and produce catalepsy in animals in a receptor-mediated fashion. Tolerance develops to the motor effects of delta 9-THC after repeated administration. To test the hypothesis that tolerance is mediated by changes in cannabinoid receptor binding characteristics, we used quantitative in vitro autoradiography of [3H]CP-55,940 binding to striatal brain sections from rats treated either chronically or acutely with delta 9-THC, CP-55,940, or the inactive natural cannabinoid cannabidiol. In the chronic conditions, rats were given daily i.p. injections of delta 9-THC (10 mg/kg), cannabidiol (10 mg/kg), or CP-55,940 (1, 3, or 10 mg/kg) for 2 weeks and sacrificed 30 min after the last injection. In the acute condition, animals received a single dose (10 mg/kg) prior to sacrifice. Rats developed tolerance to the inhibitory effects of delta 9-THC and CP-55,940, assayed in an open field on days 1, 7, and 14. Cannabidiol had no effect on behavior. Densitometry of [3H]CP-55,940 binding to brain sections showed that delta 9-THC- and CP-55,940-treated animals had homogeneous decreases in binding in all structures measured at the selected striatal levels. Cannabidiol had no effect on binding. Analysis of binding parameters showed that alterations in the acute condition were attributed to changes in affinity (KD), whereas the major changes in the chronic condition were attributed to a lowering of capacity (Bmax). The effects in the 1, 3, and 10 mg/kg CP-55,940 conditions were dose-dependent and paralleled the behavioral data showing that the animals given the highest dose developed the greatest degree of tolerance. The data suggest that tolerance to cannabinoids results at least in part from agonist-induced receptor down-regulation. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/8395305/Chronic_cannabinoid_administration_alters_cannabinoid_receptor_binding_in_rat_brain:_a_quantitative_autoradiographic_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0006-8993(93)90220-H DB - PRIME DP - Unbound Medicine ER -