The phenomenon of contingent tolerance to carbamazepine (CBZ) during amygdala-kindled seizure development was discovered by Dr. Weiss of the Section on Psychobiology. We have begun autoradiographic studies of various receptors to investigate the biochemical mechanism of this contingent tolerance to CBZ. The assays have been performed but the image analysis is still in progress. The following neurotransmitter receptors were assayed. 1) Glutamate NMDA subtype with [3H]MK-801. 2) GABA with [3H]muscimol. 3) Central-type benzodiazapine with [3H]Ro 15-788. 4) Peripheral-type benzodiazepine with [3H]Ro 5-4864. 5) Adenosine A1 and A2a subtypes with [3H]cyclohexyladenosine and [3H]CGS-21680, respectively. Thus far, film analysis has confirmed that the GABA A and central-type benzodiazepine receptors show increased binding in the dentate gyrus of the hippocampus with electrical kindling of the amygdala. No conclusions as to the effects of kindling or contingent tolerance to CBZ can be drawn at this time for the other receptor systems. These results await further analysis of the autoradiographic film images.
