Age‐Related Differences in the Effects of GABA, Agonists Microinjected Into Rat Substantia Nigra: Pro‐ and Anticonvulsant Actions

Summary: GABAergic transmission in the substantia nigra pars reticulata (SNR) has an important role in the control of experimental seizures. In the flurothyl seizure model, SNR microinjection of the selective GABA, receptor agonist muscimol results in a biphasic dose‐response curve in adults: Intermediate doses are anticonvulsant, but high doses have proconvulsant effects. Another GABA_A agonist, THIP (4,5,6,7‐tetrahydroisox‐azolo‐[5,4‐c]pyndin‐3‐01), also produces anticonvulsant effects at lower doses, whereas higher doses tend to produce a proconvulsant effect. In 16‐day‐old rat pups, no Both clinically and experimentally, it is recognized that the immature brain is at increased risk for sustaining epileptic seizures, particularly generalized seizures (1). An important goal of neuroscience research is to identify the neuronal circuitry and synaptic pharmacology underlying this ontogenic phenomenon. Such understanding will help direct the development of more efficacious and selective age‐specific therapies than those currently available.