title: Chronic Δ9-Tetrahydrocannabinol during Adolescence Differentially Modulates Striatal CB1 Receptor Expression and the Acute and Chronic Effects on Learning in Adult Rats.
abstract: The purpose of this study was to determine whether chronic administration of Δ(9)-tetrahydrocannabinol (THC) during adolescence would (1) modify any sex-specific effects of THC on learning and (2) affect the development of tolerance to THC as an adult. Male and female rats received daily injections of saline or 5.6 mg/kg of THC from postnatal day 35-75, yielding four groups (female/saline, female/THC, male/saline, and male/THC). Rats were then trained on a procedure that assayed both learning and performance behavior and administered 0.32-18 mg/kg of THC acutely as adults (experiment 1). THC produced rate-decreasing and error-increasing effects in both sexes; however, female rats were more sensitive than male rats were to the rate-decreasing effects. Rats were then chronically administered 10 mg/kg of THC (experiment 2). Rats that received THC during adolescence developed tolerance to the rate-decreasing effects more slowly and less completely than did rats that received saline; in addition, females developed tolerance to the error-increasing effects of THC slower than males did. Western blot analysis of brain tissue indicated long-term changes in hippocampal and striatal cannabinoid type-1 receptor (CB1R) levels despite levels that were indistinguishable immediately after chronic treatment during adolescence. Striatal CB1R levels were increased in adult rats that received THC during adolescence; hippocampal CB1R levels varied by sex. In summary, female rats were more sensitive than male rats were to the acute and chronic effects of THC, and chronic administration of THC during adolescence produced long-term changes in CB1R levels that correlated with decreased tolerance development to the rate-decreasing effects of THC.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (P.F.W., M.J.K., P.J.W.), Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (P.F.W.), and Department of Pharmacology, Howard University, Washington, D.C. (C.M.F.).
authors.forename: Peter F
authors.initials: PF
authors.lastname: Weed
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (P.F.W., M.J.K., P.J.W.), Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (P.F.W.), and Department of Pharmacology, Howard University, Washington, D.C. (C.M.F.).
authors.forename: Catalin M
authors.initials: CM
authors.lastname: Filipeanu
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (P.F.W., M.J.K., P.J.W.), Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (P.F.W.), and Department of Pharmacology, Howard University, Washington, D.C. (C.M.F.).
authors.forename: Myles J
authors.initials: MJ
authors.lastname: Ketchum
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (P.F.W., M.J.K., P.J.W.), Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (P.F.W.), and Department of Pharmacology, Howard University, Washington, D.C. (C.M.F.) pwinsa@lsuhsc.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Winsauer
mesh_terms: D000375:Aging / Q000523:psychology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004361:Drug Tolerance; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007858:Learning / Q000187:drug effects*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis* / Q000187:drug effects; D012727:Sex Characteristics
chemical_list: D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol