title: GABA system changes in methylphenidate sensitized female rats.
abstract: Methylphenidate (MPD) is a psychostimulant that is prescribed to treat attention-deficit/hyperactivity disorder (ADHD) and has been used as a recreational drug. In animal models, repetitive exposure to methylphenidate can induce a behavioral sensitization. Stimulants are able to change neuronal circuits in the mesolimbic pathway, and the GABA system is one of the most involved neurotransmitter systems in this process. Women represent a risk group for psychostimulant abuse because they respond more strongly, which is probably due to the influence of sex hormones. The objective of the present study was to investigate the influence of sex hormones on behavioral sentsitization and changes to glutamic acid decarboxylase (GDA65 and GDA67) isoenzymes and α2 GABAA receptor subunit mRNA expression in the prefrontal cortex and the striatum of rats, as induced by methylphenidate administration (2.5 mg/kg, i.p.). Female rats were divided into 2 hormonal conditions: ovariectomized and intact group. Repeated methylphenidate treatment led to behavioral sensitization, which was stronger in females with circulating hormones (intact group). The analysis of mRNA levels in the striatum, in both groups, showed a decline in GAD65, but not GAD67, transcription after repeated methylphenidate treatment. In the prefrontal cortex, both GAD65 and GAD67 showed an increase in transcription with repeated methylphenidate treatment. There was no change in the transcription level of α2 GABAA receptor subunits. In conclusion, it was shown that sex hormones were able to modify behavioral sensitization to methylphenidate and the drug affected the GABA system in brain areas known to be involved in the development of drug dependence.
authors.affiliation: Division of Pharmacology, Basic Health Sciences Department, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil. freese@ufcspa.edu.br
authors.forename: L
authors.initials: L
authors.lastname: Freese
authors.forename: E J
authors.initials: EJ
authors.lastname: Muller
authors.forename: M F
authors.initials: MF
authors.lastname: Souza
authors.forename: N S
authors.initials: NS
authors.lastname: Couto-Pereira
authors.forename: C F
authors.initials: CF
authors.lastname: Tosca
authors.forename: M
authors.initials: M
authors.lastname: Ferigolo
authors.forename: H M T
authors.initials: HM
authors.lastname: Barros
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase