A 'crash' course on psychostimulant withdrawal as a model of depression

Most drugs of abuse generate diverse behavioral and neurochemical effects in mammals. However, one feature common to many such drugs is the phenomenon of the withdrawal syndrome that results from termination of drug administration. Early drug withdrawal, often referred to as the 'crash' phase in humans, is characterized by adverse psychological and/or somatic symptoms. Withdrawal from psychostimulant drugs precipitates a transient and primarily psychological condition that bears remarkable similarity to the symptoms of major depressive disorder in humans. Rodent paradigms of psychostimulant withdrawal faithfully model the human condition. Associated behavioral deficits in these animals can be reversed by treatments with antidepressant properties, suggesting that psychostimulant withdrawal might provide the basis for an animal model of depression. Current advances and limitations in the development of this model, together with recent evidence that psychostimulant withdrawal in rodents can be used to screen for novel, rapidly acting antidepressant treatments, are discussed.