The stereotyped behavior syndrome: a new model and proposed therapy

The stereotyped behavior syndrome was induced in rats through local impairment of inhibitory GABA-ergic mechanisms in both caudate nuclei by bilateral microinjection of tetanus toxin, penicillin, or picrotoxin into the rostral part of the caudate nucleus. Intraperitoneally injected haloperidol suppressed the syndrome; this effect was dose-dependent. The same effect on the tetanus toxin-induced stereotyped behavior was produced by GABA microinjected bilaterally into the rostral part of the caudate nucleus of unrestrained rats. It was found in this model of tetanus toxin-induced stereotyped behavior that lithium chloride and diazepam can suppress the syndrome. Combined application of lithium chloride, diazepam, and haloperidol in minimal effective doses resulted in a much more complete and longer-lasting suppression of the syndrome than the separate use of these drugs. This effect is attributed to the joint specific actions of the drugs on pathogenetically interrelated components of a hyperactive determinant structure that arises in the caudate nuclei after impairment of the GABA control and this is responsible for the stereotyped behavior syndrome.