title: Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates.
abstract: Few and often contradictory reports exist on the long-term neurobiological consequences of cannabinoid consumption in adolescents. The endocannabinoid system plays an important role during the different stages of brain development as cannabinoids influence the release and action of different neurotransmitters and promote neurogenesis. This study tested whether long-lasting interference by cannabinoids with the developing endogenous cannabinoid system during adolescence caused persistent behavioral alterations in adult rats. Adolescent female and male rats were treated with increasing doses of Delta(9)-tetrahydrocannabinol (THC) for 11 days (postnatal day (PND) 35-45) and left undisturbed until adulthood (PND 75) when behavioral and biochemical assays were carried out. CB1 receptor level and CB1/G-protein coupling were significantly reduced by THC exposure in the amygdala (Amyg), ventral tegmental area (VTA) and nucleus accumbens (NAc) of female rats, whereas male rats had significant alterations only in the amygdala and hippocampal formation. Neither female nor male rats showed any changes in anxiety responses (elevated plus maze and open-field tests) but female rats presented significant 'behavioral despair' (forced swim test) paralleled by anhedonia (sucrose preference). In contrast, male rats showed no behavioral despair but did present anhedonia. This different behavioral picture was supported by biochemical parameters of depression, namely CREB alteration. Only female rats had low CREB activity in the hippocampal formation and prefrontal cortex and high activity in the NAc paralleled by increases in dynorphin expression. These results suggest that heavy cannabis consumption in adolescence may induce subtle alterations in the emotional circuit in female rats, ending in depressive-like behavior, whereas male rats show altered sensitivity to rewarding stimuli.
authors.affiliation: DBSF, Pharmacology Section, and Neuroscience Center, University of Insubria, Varese, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rubino
authors.forename: Daniela
authors.initials: D
authors.lastname: Vigano'
authors.forename: Natalia
authors.initials: N
authors.lastname: Realini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Guidali
authors.forename: Daniela
authors.initials: D
authors.lastname: Braida
authors.forename: Valeria
authors.initials: V
authors.lastname: Capurro
authors.forename: Chiara
authors.initials: C
authors.lastname: Castiglioni
authors.forename: Francesca
authors.initials: F
authors.lastname: Cherubino
authors.forename: Patrizia
authors.initials: P
authors.lastname: Romualdi
authors.forename: Sanzio
authors.initials: S
authors.lastname: Candeletti
authors.forename: Mariaelvina
authors.initials: M
authors.lastname: Sala
authors.forename: Daniela
authors.initials: D
authors.lastname: Parolaro
mesh_terms: D000367:Age Factors; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D013759:Dronabinol / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
chemical_list: D013759:Dronabinol