Effect of nifedipine on alprazolam - induced anxiolysis and brain GABA level changes in albino rats

OBJECTIVE: The present study investigates the effects of alprazolam (ALP) and nifedipine alone or in combination on behavior and on g-aminobutyric acid (GABA) levels, in discrete brain regions of albino rats.

METHODS: The anxiolytic effect was studied using a plus maze model and brain levels of GABA were measured using high performance liquid chromatography. Four acute treatment groups of rats were used. In the first they were treated with 1% Tween 80 (1ml/kg), in the second with nifedipine (10mg/kg), in the third with ALP (2mg/kg) and in the fourth with ALP in addition to nifedipine in the respective doses. The work was carried out at the Faculty of Pharmacy of Al-Fateh University, Tripoli, Libya in the first half of 2002.

RESULTS: The results indicate that the anxiolytic effect of ALP was not modified by nifedipine. Nifedipine by itself significantly decreased the motor activity (decrease in total lines crossed), this effect was apparently antagonized by ALP. Alprazolam administration produced an increase of GABA levels in cerebellum and striatum and a decrease in the brain stem. Nifedipine per-se had no effect on GABA levels in the brain stem but it partially antagonized ALP-induced inhibitory effect on GABA in this region. Alprazolam significantly increased GABA levels in the striatum, while nifedipine alone had no effect on neurotransmitter levels and did not modify the ALP effect in this brain region. Alprazolam or nifedipine had no significant effect on GABA levels in midbrain, cerebral cortex and whole brain. There were no significant changes in GABA levels in midbrain and whole brain with drug combination. However, the combination decreased GABA levels significantly in the cerebral cortex.

CONCLUSION: It may be concluded that, the anxiolytic effect of ALP possibly occurs through changes in brain GABA levels (an increase in cerebellum and striatum with a decrease in brain stem). The effect was not modified by nifedipine which per se had no affect on GABA levels in any brain area. The significant decrease in GABA levels in cerebral cortex by ALP-nifedipine combination may be due to the mutual closure of calcium channel (mentioned in literature) resulting in inhibition of the EAA-ergic input to GABA-ergic neuron.