Novelty and habituation: relation with ACh and GABA release from the cerebral cortex and hippocampus of the rat

A consensus has been reached on the role of the forebrain cholinergic system in arousal and attention. Evidences indicate that GABA may be involved in cognitive mechanisms through its modulatory action on the cholinergic system. Aim of this work was to investigate the activity of cholinergic, GABAergic and glutamatergic systems during novelty and habituation measuring ACh, GABA and glutamate release in the cerebral cortex and dorsal hippocampus of rats. Rats, implanted with a microdialysis probe either in the cortex or hippocampus were placed in an arena twice consecutively (Arena I and II, 30 min each, spaced by 60 min) and neurotransmitter release as well as motor activity were measured. During the two explorations of the arena, cortical and hippocampal ACh release showed a TTX-dependent increase, which was higher during Arena I than during Arena II and was more pronounced and long-lasting in the hippocampus than in the cortex. Motor activity was higher during the first 10 min of exploration of both Arena I and Arena II, gradually decreased during the further 20 min and correlated significantly with cortical ACh release. Cortical GABA release increased during Arena II only but was not correlated to motor activity. Hippocampal GABA release was variable, increasing in 2 out of 7 rats only. Cortical and hippocampal glutamate release did not change during the two explorations of the arena. These data indicate that during exploration of a novel environment cortical and hippocampal cholinergic pathways are activated, and the cortical GABAergic system may act as an inhibitory brake on cortical cholinergic activity during habituation.