Behavioral and neurochemical effects of apomorphine in the cat

Administration of apomorphine (2-10 mg/kg i.p.) elicited a number of behaviors, such as limb flicking, abortive grooming, investigatory and hallucinatory-like responses, head and body shakes, and excessive grooming, which we have previously proposed as an animal model for studying the actions of LSD and related hallucinogens. Repeated administration of apomorphine resulted in a significant tolerance, which occurred within 2 h of the initial injection, and completely dissipated within 24 h. A pronounced LSD-apomorphine cross tolerance was observed; however, there was no significant apomorphine-LSD tolerance. Apomorphine-induced behavioral changes were blocked by prior treatment with haloperidol, but were unchanged by pretreatment with L-DOP[A. Administration of L-DOPA, in combination with a peripheral decarboxylase inhibitor, did not elicit these characteristic behavioral changes. Increasing synaptic serotonin levels by monoamine oxidase inhibition, precursor administration, or reuptake blockade in general did not alter the behavioral response to apomorphine. Similarly, pretreatment with serotonin receptor blockers produced no large changes in apomorphine-induced behaviors. Prior serotonin depletion with chronic p-chlorophenylalanine administration, however, potentiated certain apomorphine-induced behaviors. Neurochemical studies revealed that apomorphine administration increased striatal dopamine, and decreased dopamine metabolites. Norepinephrine levels were generally decreased throughout the CNS by apomorphine treatment. Administration of apomorphine increased CNS serotonin and 5-hydroxyindoleacetic acid levels, while tryptophan levels were unchanged. The biological bases of the limb flick model is discussed in the context of these pharmacological and neurochemical studies.