title: Cross-substitution of Δ9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats.
abstract: Synthetic indole-derived cannabinoids, originally developed to probe cannabinoid CB1 and CB2 receptors, have become widely abused for their marijuana-like intoxicating properties. The present study examined the effects of indole-derived cannabinoids in rats trained to discriminate Δ(9)-tetrahydrocannabinol (Δ(9)-THC) from vehicle. In addition, the effects of Δ(9)-THC in rats trained to discriminate JWH-018 from vehicle were assessed. Adult male Sprague-Dawley rats were trained to discriminate 3mg/kg Δ(9)-THC or 0.3mg/kg JWH-018 from vehicle. JWH-018, JWH-073, and JWH-210 fully substituted in Δ(9)-THC-trained rats and Δ(9)-THC substituted in JWH-018-trained rats. In contrast, JWH-320, an indole-derived cannabinoid without affinity for CB1 receptors, failed to substitute for Δ(9)-THC. Pre-treatment with 1mg/kg rimonabant significantly reduced responding on the JWH-018-associated lever in JWH-018-trained rats. These results support the conclusion that the interoceptive effects of Δ(9)-THC and synthetic indole-derived cannabinoids show a large degree of overlap, which is predictive of their use for their marijuana-like intoxicating properties. Characterization of the extent of pharmacological differences among structural classes of cannabinoids, and determination of their mechanisms remain important goals.
authors.affiliation: RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA. Electronic address: jwiley@rti.org.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Wiley
authors.affiliation: RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lefever
authors.affiliation: RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Cortes
authors.affiliation: RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Marusich
mesh_terms: D000818:Animals; D004192:Discrimination, Psychological; D013759:Dronabinol / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007211:Indoles; D009281:Naphthalenes; D013759:Dronabinol; C552597:1-pentyl-3-(1-naphthoyl)indole
keywords: Discriminative stimulus; JWH-018; JWH-073; JWH-210; Synthetic cannabinoids; Δ(9)-tetrahydrocannabinol