Habituation of the local cyclic GMP response during amygdaloid carbachol kindling in the rat.

Seizures kindled with amygdaloid carbachol injections are transynaptic, dependent on activation of a specific population of muscarinic receptors, and some components of their expression could be mediated by intracellular second messengers. We measured cyclic GMP and cyclic AMP concentrations in micropunch biopsies of multiple brain regions after microwave fixation during the development and the expression of carbachol-kindled seizures in the rat. In the naive carbachol-injected amygdala, cyclic GMP concentrations rose from 1.03 +/- 0.15 pmol/mg protein to 2.21 +/- 0.46 after 2 min, and significant rises occurred in caudate, hypothalamus and contralateral amygdala. This response did not occur in implanted controls, after injection of mock cerebrospinal fluid, or when carbachol actions were blocked with atropine. The rise in cyclic GMP progressively disappeared upon repeated stimulation (injected amygdala on tenth stimulation: 0.72 +/- 0.23 pmol/mg protein). However, a late rise in both cyclic GMP and cyclic AMP concentrations occurred in many brain regions during convulsive seizures. These data suggest that during the development of kindling, changes in neuronal and synaptic excitability are associated with changes in intracellular second messengers.