Selective Involvement of the Neurotransmitter Systems of the Cerebellum in the Mechanisms Forming Different Types of Defensive Behavior

Abstract

The extracellular contents of neurotransmitter amino acids, along with the total serotonin plus its metabolite 5-hydroxyindoleacetic acid (5-HIAA) content, in the rat cerebellar vermis were studied by microdialysis at different stages of the formation of long-term extinction of an acoustic startle reaction and conditioned contextual freezing in a startle chamber before the onset of sound stimulation. GABA and serotonin contents were found to increased 10 min after the end of training, with increases in glutamate and glycine levels at 24 h, which were accompanied by decreases in serotonin plus 5-HIAA levels in the cerebellar vermis. Positive correlations were seen between GABA and glycine levels during training and the formation of conditioned freezing, as well as between the glutamate level during testing and extinction of the orientational component of the acoustic startle reaction. Application of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist 2-amino-5-phosphovaleric acid (APV) before training was found to suppress, while the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) stimulated long-term habituation of the orientational-investigative component of the acoustic startle reaction. The GABA receptor antagonists bicuculline and faclofen, used in the same conditions, suppressed long-term extinction of the defensive component of the acoustic startle reaction and the formation of conditioned contextual freezing. The serotonin receptor antagonist ritanserin, applied to the cerebellar vermis before training, impaired the formation of long-term memory of conditioned freezing and extinction of the defensive component of the acoustic startle reaction, while administration 1 h before testing stimulated extinction of the defensive component of the acoustic startle reaction. These data provide evidence that the mechanisms of long-term habituation of the orientational component of the acoustic startle reaction are associated the levels of activity of glutamatergic synaptic processes in the cerebellum, while serotoninergic terminals and GABAergic interneurons are involved in the process of the long-term extinction of the defensive component of the acoustic startle reaction and the formation of conditioned contextual fear.