Neuromediators and defensive responses including tonic immobility (TI): Brain areas and circuits involved.

Serotonin, acetylcholine and GABA are the neuromediators most involved in tonic immobility (TI). TI duration, in fact, decreases in rabbits following systemic serotonin administration and in guinea pigs following serotonin microinjection administration into the amygdala owing to the activation of fear-related GABAergic inhibitory mechanisms. On the other hand, repeated TI inductions in rabbits and guinea pigs reduce brain serotonin turnover in several brain areas. Microinjections of the acetylcholine agonist carbachol into amygdala, hypothalamus and PAG increase TI duration and reduces other defensive responses to threatening stimuli in several animal species. The cholinergic and serotonergic systems exert different effects on TI in different regions of the PAG according to the receptors stimulated. Their combined action activates opioid-GABAergic neurons ultimately affecting TI duration. Mammals TI and human cataplexy are innate responses induced by different stimuli, although both characterized by deficiency in orexin, reduced muscle tone, normal jerk reflexes and preserved consciousness.