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GABA system changes in methylphenidate sensitized female rats.

L Freese¹, E J Muller, M F Souza

¹Division of Pharmacology, Basic Health Sciences Department, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil. freese@ufcspa.edu.br

Behavioural Brain Research

|March 31, 2012

Summary

Sex hormones amplify methylphenidate (MPD) behavioral sensitization in female rats, altering GABA system gene expression in the brain. This highlights hormonal influences on stimulant drug responses and dependence.

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Area of Science:

Neuroscience
Pharmacology
Endocrinology

Background:

Methylphenidate (MPD) is a psychostimulant used for ADHD and recreationally, known to induce behavioral sensitization.
The GABA system is critically involved in stimulant-induced neurocircuitry changes in the mesolimbic pathway.
Women exhibit heightened responses to psychostimulants, potentially due to sex hormone influence.

Purpose of the Study:

To investigate the impact of sex hormones on MPD-induced behavioral sensitization.
To examine MPD's effects on glutamic acid decarboxylase (GAD65/GAD67) and α2 GABAA receptor subunit mRNA expression.
To determine if hormonal status influences these neurochemical changes in female rats.

Main Methods:

Female rats were divided into intact (hormonal) and ovariectomized (hormone-deficient) groups.
MPD (2.5 mg/kg, i.p.) was administered repeatedly to induce behavioral sensitization.
mRNA expression of GAD65, GAD67, and α2 GABAA receptor subunits was analyzed in the prefrontal cortex and striatum.

Main Results:

Repeated MPD administration induced behavioral sensitization, which was significantly stronger in intact female rats.
MPD treatment decreased GAD65 mRNA in the striatum but increased both GAD65 and GAD67 mRNA in the prefrontal cortex.
No significant changes were observed in α2 GABAA receptor subunit mRNA levels.

Conclusions:

Sex hormones modulate behavioral sensitization to methylphenidate in female rats.
MPD alters GABA system gene expression in brain regions associated with drug dependence.
These findings underscore the role of hormonal fluctuations in psychostimulant sensitivity and abuse potential.