title: Framework for sex differences in adolescent neurobiology: a focus on cannabinoids.
abstract: This review highlights the salient findings that have furthered our understanding of how sex differences are initiated during development and maintained throughout life. First we discuss how gonadal steroid hormones organize the framework for sex differences within critical periods of development-namely, during those exposures which occur in utero and post-partum, as well as those which occur during puberty. Given the extensive precedence of sex differences in cannabinoid-regulated biology, we then focus on the disparities within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabinoid CB(1) receptors is regulated throughout development. This is followed by a discussion of differential vulnerability to the pathological sequelae stemming from cannabinoid exposure during adolescence. Next we talk about sex differences in the interactions between cannabinoids and other drugs of abuse, followed by the organizational and activational roles of gonadal steroids in establishing and maintaining the sex dependence in the biological actions of cannabinoids. Finally, we discuss ways to utilize this knowledge to strategically target critical developmental windows of vulnerability/susceptibility and thereby implement more effective therapeutic interventions for afflictions that may be more prevalent in one sex vs. the other.
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, C/Jose Antonio Novais no. 2, Madrid, Spain. pazviver@bio.ucm.es
authors.forename: Maria-Paz
authors.initials: MP
authors.lastname: Viveros
authors.forename: Eva M
authors.initials: EM
authors.lastname: Marco
authors.forename: Meritxell
authors.initials: M
authors.lastname: López-Gallardo
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Wagner
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000293:Adolescent; D041923:Adolescent Development / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology*; D003423:Critical Period, Psychological; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000502:physiology; D012737:Sex Factors; D046468:Sexual Development / Q000187:drug effects* / Q000502:physiology
chemical_list: D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D012739:Gonadal Steroid Hormones; D043882:Receptors, Cannabinoid