Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis

摘要: Some people who repeatedly use stimulant drugs, such as amphetamine (AMPH), develop an AMPH-induced psychosis that is similar to paranoid schizophrenia. There has been, therefore, considerable interest in characterizing the effects of chronic drug treatment on brain and behavior non-human animals, developing animal model AMPH psychosis. A review this literature shows animals can produce at least two different syndromes, both these have been proposed models The first syndrome called 'AMPH neurotoxicity', produced by maintaining elevated concentrations for prolonged periods time. neurotoxicity characterized what termed 'hallucinatory-like' behavior, which occurs association with damage resulting depletion striatal DA other monoamines. second 'behavioral sensitization', repeated intermittent administration lower doses AMPH. Behavioral sensitization a progressive enduring enhancement many behaviors, not accompanied or monoamine depletion. It argued changes associated phenomenon behavioral provide better 'model' than those neurotoxicity. Much involves critical analysis hypotheses regarding biological basis sensitization. Research question focused mesotelencephalic systems, suggestions by: increase postsynaptic receptors; synthesis; utilization and/or release; decrease autoreceptors, are evaluated. concluded there convincing evidence receptors synthesis sensitized In contrast, strong support notion due enhanced release, especially upon re-exposure drug. release autoreceptor subsensitivity was found be equivocal, therefore should entertained. Lastly, discussed idea unique psychopharmacology but may environmental stimuli directly indirectly activate catecholamine systems.(ABSTRACT TRUNCATED AT 400 WORDS)