Adolescent self-administration of the synthetic cannabinoid receptor agonist JWH-018 induces neurobiological and behavioral alterations in adult male mice.
Psychopharmacology (Berl)
; 239(10): 3083-3102, 2022 Oct.
Article
en En
| MEDLINE
| ID: mdl-35943523
ABSTRACT
RATIONALE The use of synthetic cannabinoid receptor agonists (SCRAs) is growing among adolescents, posing major medical and psychiatric risks. JWH-018 represents the reference compound of SCRA-containing products. OBJECTIVES:
This study was performed to evaluate the enduring consequences of adolescent voluntary consumption of JWH-018.METHODS:
The reinforcing properties of JWH-018 were characterized in male CD1 adolescent mice by intravenous self-administration (IVSA). Afterwards, behavioral, neurochemical, and molecular evaluations were performed at adulthood.RESULTS:
Adolescent mice acquired operant behavior (lever pressing, Fixed Ratio 1-3; 7.5 µg/kg/inf); this behavior was specifically directed at obtaining JWH-018 since it increased under Progressive Ratio schedule of reinforcement, and was absent in vehicle mice. JWH-018 IVSA was reduced by pretreatment of the CB1-antagonist/inverse agonist AM251. Adolescent exposure to JWH-018 by IVSA increased, at adulthood, both nestlet shredding and marble burying phenotypes, suggesting long-lasting repetitive/compulsive-like behavioral effects. JWH-018 did not affect risk proclivity in the wire-beam bridge task. In adult brains, there was an increase of ionized calcium binding adaptor molecule 1 (IBA-1) positive cells in the caudate-putamen (CPu) and nucleus accumbens (NAc), along with a decrease of glial fibrillary acidic protein (GFAP) immunoreactivity in the CPu. These glial alterations in adult brains were coupled with an increase of the chemokine RANTES and a decrease of the cytokines IL2 and IL13 in the cortex, and an increase of the chemokine MPC1 in the striatum.CONCLUSIONS:
This study suggests for the first time that male mice self-administer the prototypical SCRA JWH-018 during adolescence. The adolescent voluntary consumption of JWH-018 leads to long-lasting behavioral and neurochemical aberrations along with glia-mediated inflammatory responses in adult brains.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quimiocina CCL5
/
Agonistas de Receptores de Cannabinoides
Límite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia