Elevated GABA levels in the medial prefrontal cortex and lower estrogen levels abolish cocaine sensitization behavior in ovariectomized female rats

• Published in: Brain research 2020-12, Vol.1749, p.147144, Article 147144
• Main Authors: Freese, Luana, Fraga de Souza, Marilise, Schüler Nin, Maurício, Calleti, Greice, Flores Peres, Valéria, Gomez, Rosane, Maria Tannhauser Barros, Helena
• Format: Article
• Language: English
• Subjects: Drug addiction; Glutamate; Locomotion; Microdialysis; Taurine
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2020.147144

[Display omitted] •Timely and high GABA efflux in the mPFC suppresses the behavioral response of cocaine sensitization in ovariectomized rats.•Glutamate and taurine efflux increase in the mPFC after acute cocaine administration.•Lower GABA levels are associated with increased behavioral sensitization of cocaine in intact female rats.•Glutamate and taurine are not related to cocaine behavioral sensitization.•Elevated estrogen levels increase behavioral cocaine-sensitized response in female rats. Animal models show that cocaine sensitization, a behavioral marker of addiction, is more significant in intact gonadal female than male rats and ovariectomy suppress this behavior in female rats. However, few studies explore changes in neurotransmission related to this phenomenon. Here we investigated the in vivo changes on GABA, glutamate, and taurine levels in the medial prefrontal cortex (mPFC) of gonadal intact or ovariectomized female rats after a cocaine challenge administration. Adult female rats were bilaterally ovariectomized (OVX), or sham-operated (SHAM) and randomly assigned to control (CTR), acute (ACT), or repeated (RPT) cocaine administration groups. In the challenge day, after eight days of daily cocaine (15 mg/kg) or saline administration and ten days of washout and stereotaxic surgery, RPT and ACT groups received cocaine, and the CTR group received saline. Horizontal locomotion was monitored concomitantly with microdialysate collection to determine extracellular GABA, glutamate, and taurine levels. Hormonal determination in blood samples confirmed the lower hormonal status of the OVX. Cocaine sensitization occurred in SHAM-RPT female rats after the challenge administration. Non-sensitized OVX-RPT rats showed a peak of GABA at 30 min after cocaine administration, with no change on glutamate and taurine levels. Therefore, elevated GABA levels in the mPFC and lower serum estrogen levels abolish cocaine sensitization behavior in ovariectomized female rats. We discuss some possible implications of these finding for future models of cocaine sensitization research lighting in the female hormonal influence.