Anticonvulsant effects of GABA(A) modulators microinfused into area tempestas or substantia nigra in rats exposed to soman

Abstract

Enhancement of GABAergic neurotransmission has anticonvulsant effects against nerve agent-induced seizures. However, systemic administration of drugs with GABA(A) agonist-like effects does not differentiate well between their anticonvulsant impact. In the present study, GABA(A) modulating drugs (1 microl) were microinfused bilaterally into the seizure controlling substrates, substantia nigra (SN) or area tempestas (AT), of rats subjected to seizures induced systemically by soman (100 microg/kg). The results showed that infusion of ethanol (0.47 micromol) and propofol (20 microg) in both SN and AT icrohad anticonvulsant effects (prevention of seizures or increased latency to seizures). Anticonvulsant effects were also obtained when muscimol (120 ng) was infused into AT or when diazepam (5 microg) was infused into SN. Pentobarbital (50 microg) did not attenuate soman-elicited seizures in any of the injection sites. Results from control experiments showed that the effects from the microinfusions were site-specific, and that the absence of effects of pentobarbital was not a result of too low dose of the drug. The microinfusion technique may allow a more detailed examination of anticonvulsant properties of drugs than by the use of systemic administration.