Effect of kainic acid injections and other brain lesions on vasoactive intestinal peptide (VIP)-stimulated formation of cAMP in rat brain

Abstract

In rat striatal slices, both intrastriatal kainic acid injection, which destroys striatal neurones, and intranigral injection of 6-hydroxydopamine (6-OHDA), which leads to a degeneration of dopamine nerve terminals in the striatum, reduced vasoactive intestinal peptide (VIP)-induced cAMP accumulation by approximately 60%. Cortical ablation, which leads to degeneration of cortico-striatal fibres, had no effect on striatal VIP-induced cAMP formation. Knife cut lesions transecting the stria terminalis, which destroy afferent fibres to the amygdala, decreased the VIP-induced increase in cAMP in amygdala slices by 40%, while kainic acid injection into the amygdala had no effect. Kainic acid injection into several other brain regions, including hippocampus, cortex and hypothalamus also failed to affect the VIP-elicited increase in cAMP in slices, despite reductions in choline acetyl-transferase, glutamate decarboxylase, cyclic nucleotide phosphodiesterase and basal levels of cAMP. The results of a study of the effects of various VIP fragments on cAMP stimulation in striatal and cortical slices suggests that the entire sequence of VIP is necessary for full activity. The results suggest that VIP may be involved in neuromodulation or neurotransmission in the striatum and/or nigrostriatal pathway and also in the stria terminalis from the bed nucleus to the amygdala.