Elliot Valenstein - US grants

Studies of the long-lasting behavioral and biochemical effects of temporal lobe seizures will be pursued using the kindling model. Kindling refers to the progressive development of seizures and clonic convulsions in response to brief electrical brain stimulation. Inbred mice given amygdala stimulation until they respond regularly with generalized convulsions have shown a striking and long-lasting increase in sensitivity to morphine that is blocked by naloxone. The hypothesis that seizure-proneness is correlated with changes in endogeneous opiate receptors will be investigated through experiments designed to locate the specific brain sites where changes take place and to identify the population of opiate receptors that may be involved. In other studies using kindled rats we have recently demonstrated that a regimen of gradually increasing intensities of electrical stimulation, which does not produce any afterdischarges or convulsions, can suppress convulsions for periods up to a week. Additional stimulation regimens will be explored to determine the possibility of completely reversing the kindling process or of producing a longer-lasting inhibition. Pilot studies demonstrating that kindling can modify brain asymmetries with consequent effects on rotational behavior and spatial learning will be pursued. The effects of kindling on reward systems using self-stimulation procedures in rats and on aggressive behavior in mice using the isolation paradigm will also be studied.