Changes in Cholinergic Markers Following Kainic Acid Lesion of the Ventral Globus Pallidus in Rat

Abstract: Choline acetyltransferase (CAT) and glutamate decarboxylase (GAD) activities and ³H] quinuclidinyl benzilate (³H]QNB) binding were determined in the rat frontal cortex following damage to the basal forebrain cholinergic system. Pre- and postsynaptic changes in the cholinergic system with the passage of time werealso studied. After a unilateral injection of kainic acid into the right ventral globus pallidus, the GAD levels remained unaffected, but the CAT levels decreased to 63.4% after 7 days. After 12 weeks, the CAT levels had returned to 87% of the control value. The Umaxof ³H]QNB binding for the muscarinic receptor was higher in the ipsilateral cortex up to 4 weeks. On the other hand, the K_D value at 12 weeks was higher without a change in the Bmax of the ³H]QNB binding.
These findings might indicate an ongoing compensatory receptor mechanism of denervation supersensitivity as a response to early changes in presynaptic cholinergic activity and the production of postsynaptic effect with presynaptic cholinergic damage over a long period of time.