Positive allosteric modulator of GABAB receptor alters behavioral effects but not afterdischarge progression induced by partial hippocampal kindling

NEUROPHARMACOLOGY

卷:110

Article

Leung, L. Stan¹  Jin, Miao^1,2  Chu, Liangwei¹  Ma, Jingyi¹ 

[1] Univ Western Ontario, Dept Physiol & Pharmacol, Med Sci Bldg, London, ON N6A 5C1, Canada

[2] Shanghai Univ Tradit Chinese Med, Dept Neurol, Longhua Hosp, Shanghai 200032, Peoples R China

关键词: GABA(B) receptor;    CGP7930;    Kindling;    Hippocampus;    Methamphetamine;    Locomotion;    Prepulse inhibition;    Auditory gating;   

DOI  :  10.1016/j.neuropharm.2016.07.017

来源: Elsevier

【 摘 要 】

Hippocampal seizures decreased the function of GABA(B) receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABA(B) receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABA(B) receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle kindled rats), or a GABA(B) receptor positive allosteric modulator CGP7930, at 1 mg/kg i.p. (CGP1-kindled) or 5 mg/kg i.p. (CGP5-kindled). The increase in the primary afterdischarge duration during kindling was not different among the groups. However, the CGP5-kindled group showed a lower afterdischarge starting frequency as compared to vehicle-kindled or CGPI-kindled groups. Partial hippocampal kindling (21 afterdischarges) resulted in decreased prepulse inhibition and decreased gating of hippocampal auditory evoked potentials in vehicle-kindled and CGPI-kindled rats, as compared to saline-injected non-kindled rats, recorded 3-4 days after the last afterdischarge. However, CGP5-kindled rats showed normal prepulse inhibition and hippocampal auditory gating (compared to non-kindled rats), which was significantly higher than the respective measure in vehicle-kindled rats. CGP5-kindled group also showed methamphetamine induced locomotion that was significant lower than the vehicle-kindled or CGPI-kindled group, but slightly higher than the saline-injected non-kindled rats. In conclusion, this study provides original data that a GABA(B) receptor positive allosteric modulator could therapeutically prevent or normalize some seizure-induced behavioral disruptions in a model of temporal lobe epilepsy. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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