title: Sex-specific disturbances of the glutamate/GABA balance in the hippocampus of adult rats subjected to adolescent cannabinoid exposure.
abstract: Adolescence is a period of active synaptic remodelling and plasticity and as such, a developmental phase of particular vulnerability to the effects of environmental insults. The endogenous cannabinoid system regulates central nervous system development and cannabinoid exposure during adolescence has been linked to several alterations to hippocampal-dependent processes such as cognition and emotion, which rely on intact glutamatergic and GABAergic systems. Here we show that K(+)-induced γ-amino butyric acid (GABA) release increases in the CA1 hippocampal field of Wistar rats of both sexes that were treated chronically with the cannabinoid agonist CP 55,940 (CP55940) during adolescence. GABA(B) receptors levels also increased in cannabinoid-exposed rats. In addition, CP55940-treated females exhibit reduced GABA transporter gene expression (GAT-1), increased GABA(A) receptor expression, as well as decreased K(+)-induced glutamate release and NMDA receptor levels. CP55940 administration did not affect the glial (EAAT2) or neuronal (EAAT3) glutamate transporter gene expression in either males or females, and nor were any changes in the mGlu5 receptor protein levels observed. Taken together, these results show that while the exacerbated GABA release induced by early cannabinoid exposure may be compensated by an increment in GABA(B) receptors, which normally function as inhibitory autoreceptors, adolescent cannabinoid exposure in the females disturbs the normal balance between glutamate and GABA transmission. These observations may provide important insight into the neuronal basis of the well-documented alterations in cognitive and emotional processes induced by adolescent cannabinoid exposure.
authors.affiliation: Department of Psychobiology, School of Psychology, UNED, C/Juan del Rosal no 10, 28040 Madrid, Spain. ahiguera@psi.uned.es
authors.forename: Alejandro
authors.initials: A
authors.lastname: Higuera-Matas
authors.forename: Miguel
authors.initials: M
authors.lastname: Miguéns
authors.forename: Santiago M
authors.initials: SM
authors.lastname: Coria
authors.forename: María Amparo
authors.initials: MA
authors.lastname: Assis
authors.forename: Erika
authors.initials: E
authors.lastname: Borcel
authors.forename: Nuria
authors.initials: N
authors.lastname: del Olmo
authors.forename: Emilio
authors.initials: E
authors.lastname: Ambrosio
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D003511:Cyclohexanols; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol