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Effects of co-administration of the GABAB receptor agonist baclofen and a positive allosteric modulator of the GABAB receptor, CGP7930, on the development and expression of amphetamine-induced locomotor sensitization in rats

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Abstract

Background

Several of the behavioral effects of amphetamine (AMPH) are mediated by an increase in dopamine neurotransmission in the nucleus accumbens. However, evidence shows that γ-aminobutyric acid B (GABAB) receptors are involved in the behavioral effects of psychostimulants, including AMPH. Here, we examined the effects of co-administration of the GABAB receptor agonist baclofen and a positive allosteric modulator of theGABAB receptor, CGP7930, on AMPH-induced locomotor sensitization.

Methods

In a series of experiments, we examined whether baclofen (2.0, 3.0 and 4.0 mg/kg), CGP7930 (5.0, 10.0 and 20.0 mg/kg), or co-administration of CGP7930 (5.0, 10.0 and 20.0 mg/kg) with a lower dose of baclofen (2.0 mg/kg) could prevent the development and expression of locomotor sensitization produced by AMPH (1.0 mg/kg).

Results

The results showed that baclofen treatment prevented both the development and expression of AMPH-induced locomotor sensitization in a dose-dependent manner. Furthermore, the positive allosteric modulator of the GABAB receptor, CGP7930, increased the effects of a lower dose of baclofen on AMPH-induced locomotor sensitization under both conditions.

Conclusion

These data provide further evidence thatGABAB receptor ligands may modulate psychostimulant-induced behaviors.

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  1. FES Iztacala, National Autonomous University of México, Av. de los Barrios 1, Los Reyes Iztacala Tlalnepantla, Edo. de México, 54090, México

    Laura N. Cedillo & Florencio Miranda

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  1. Laura N. Cedillo
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  2. Florencio Miranda
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Correspondence to Florencio Miranda.

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Cedillo, L.N., Miranda, F. Effects of co-administration of the GABAB receptor agonist baclofen and a positive allosteric modulator of the GABAB receptor, CGP7930, on the development and expression of amphetamine-induced locomotor sensitization in rats. Pharmacol. Rep 65, 1132–1143 (2013). https://doi.org/10.1016/S1734-1140(13)71471-3

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  • DOI: https://doi.org/10.1016/S1734-1140(13)71471-3

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