Drug effects on active immobility responses: what they tell us about neurotransmitter systems and motor functions

The literature reviewed indicates that active immobility can be promoted by systemic injections of various neurotransmitter systems, as follows: (1) Dopaminergic blockade of both D1 and D2 receptor subtypes. (2) Cholinergic agonism of both muscarinic and nicotinic receptors. (3) Noradrenergic agonism of both alpha-1 and alpha-2 receptors (but these agonists may interfere with haloperidol- and reserpine-induced catalepsy). (4) GABA agonism. (5) Histamine agonism, particularly at the H1 receptor. (6) Opiate agonism, including action of many endogenous opiate peptides, particularly those affecting mu and delta receptors. (7) Agonism by certain other peptides (neurotensin, cholecystokinin). Among the major interactions of neurotransmitter systems that regulate immobility, are the following: (1) Cholinergic-dopaminergic (cholinolytics disrupt catalepsy of dopaminergic blockade and dopaminergic agonists tend to disrupt cholinomimetic catalepsy). (2) Opiate-induced catalepsy is antagonized by the dopamine agonist, apomorphine, but is enhanced by amphetamine. It is also antagonized by certain alpha-2 adrenergic agonists, while it does not seem to be antagonized by anticholinergics. (3) Numerous other interactions have been reported, involving opiates and MSH, serotonin and dopamine mimetics, serotonin and ketamine, GABA and neuroleptics, neurotensin and anticholinergics and histamine. The significance of the multiple neurotransmitter systems is unknown. One possible explanation is that the various neurotransmitter systems participate in mediating the sensory inputs that are involved in triggering immobility and regulate the higher-order limbic and basal ganglia processing reactions that engage a final motor output pathway from the brainstem. The brain is assumed to contain two sets of systems, each with its own, or possibly overlapping, set of neurotransmitter systems, that promote either active immobility or locomotion. The systems reciprocally inhibit each other. Another view, not mutually exclusive, is that output from the locomotor-promoting system provides a negative feedback, via the active immobility pathways, to act as a "brake" on movement, while at the same time maintaining the muscular tonus that is characteristic of active immobility.