The problem of animal models for psychiatric conditions, as illustrated by the immobilization reaction (catalepsy) in the rat (author's transl)

Abstract

According to Venables the span of psychotic processes extends from a low level of arousal with an increased reactivity toward sensory stimuli to a high level of arousal with a reduced reactivity toward sensory stimuli. The level of arousal and the degree of reactivity, or breadth of attention, are apparently controlled by a regulatory mechanism which increases the threshold for sensory input in threatening situations. Any factor producing an electroencephalographic arousal reaction leads to a narrowing of attention. Underestimation of the size of a given object is an expression of such a reduction in the span of attention. Various authors have found a reduction in size-constancy in schizophrenics, in particular in patients exhibiting a merkedly reduced contact with their environment. A model is described in which a strong sensory stimulus induces a state of immobilization in rats treated with a low dose of morphine. Electroencephalographic recordings show that the initial state of arousal induced by peripheral stimulation is replaced by high-amplitude slow-waves and spindles as the state of immobilization develops. The current results suggest that the sensory stimulation leads to excitation of the ascending reticular formation and via the Centrum medianum and the Nucleus centralis, to activation of the striatal system, resulting in catalepsy. It would thus appear that the reticular formation and the striatum alternate in excercising a control function over the state of arousal. This would be a logical way of limiting over-reaction, which can be demonstrated most simply on the motoric response. It seems justified, therefore, to assume a relationship between catatonic stupor and the immobilization induced by stimulation. This concept is supported by the observation that of all the compounds investigated only clozapine is capable of inhibiting the immobilization in the rat model. Clozapine is a powerful antipsychotic agent with a pronounced inhibitory effect both on the reticular arousal reaction and on the schizophrenic catatonia.