title: Behavioral responses to acute and sub-chronic administration of the synthetic cannabinoid JWH-018 in adult mice prenatally exposed to corticosterone.
abstract: Recent data indicate that both availability and consumption of synthetic and natural psychoactive substances, marketed under the name of "legal highs", has increased. Among them, the aminoalkylindole-derivative JWH-018 is widely distributed due to its capability of binding the cannabinoid receptors CB1 and CB2 thereby mimicking the effects of classical drug agonists. To address whether the behavioral effects of the synthetic compound JWH-018 are similar to those induced by classical cannabinoid agonists, we investigated, in outbred CD1 mice, the consequences of its acute and sub-chronic administration (0, 0.03, 0.1, or 0.3 mg/kg, IP) at the level of body temperature, pain perception, general locomotion, and anxiety. In order to address whether the exposure to precocious stressors-modified individual reactivity to this psychoactive substance, we also investigated its effects in adult mice previously exposed to prenatal stress in the form of corticosterone supplementation in the maternal drinking water (33 or 100 mg/L). In the absence of major effects on motor coordination, JWH-018-reduced body temperature, locomotion and pain reactivity, and increased indices of anxiety. Prenatal corticosterone administration-reduced individual sensitivity to the effects of JWH-018 administration in all the aforementioned parameters. This altered response is not due to variations in JWH-018 metabolism. Present data support the hypothesis that precocious stress may affect, in the long-term, the functional status, and reactivity of the endocannabinoid system.
authors.affiliation: Section of Behavioural Neuroscience, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Macrì
authors.forename: Lara
authors.initials: L
authors.lastname: Lanuzza
authors.forename: Gustavo
authors.initials: G
authors.lastname: Merola
authors.forename: Chiara
authors.initials: C
authors.lastname: Ceci
authors.forename: Stefano
authors.initials: S
authors.lastname: Gentili
authors.forename: Antonella
authors.initials: A
authors.lastname: Valli
authors.forename: Teodora
authors.initials: T
authors.lastname: Macchia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000097:blood / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D007211:Indoles / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000523:psychology*
chemical_list: D063386:Cannabinoid Receptor Agonists; D007211:Indoles; D009281:Naphthalenes; C552597:1-pentyl-3-(1-naphthoyl)indole; D003345:Corticosterone