THERE ARE several indications that the function of central dopamine (DA) neurons is associated with schizophrenia: Amphetamine psychosis is thought to resemble schizophrenia while treatment with neuroleptic drugs are used against the disease. Amphetamine may cause DA hyperfinction by increasing DA release while neuroleptic drugs probably cause DA hypofunction as they inhibit DA receptors, It is possible to induce this state of hyperor hypofunction in animal models which may increase our understanding of the kind of functional changes that occur. The syndrome of hyperfunction, after e.g. amphetamine, is well known in animal models and associated with the typical stereotyped behaviouP while hypofunction, after neuroleptic drugs, causes a profound hypoactivity and catalepsy.’ The DA system is thrown off balance in both instances but in different directions. However, the functional effect may sometimes be the same as in the case of anorexia which is caused by amphetamine as well as neuroleptic drugs. 4 It may be speculated that normal function requires a rather narrow balance between hyper- and hypofunction. In a recent series of experiments (Ljungberg and Ungerstedt, to be published), we have studied the functional deficits occurring after a unilateral removal of the ascending DA neurons. The degeneration was induced by a stereotaxic injection of 6-hydroxydopamine (6-OH-DA) in among the DA cell bodies in the substantia nigra.2s5 The animals were tested for their ability to orient towards visual, auditory, olfactory and tactile stimuli to either side of the body. The unilaterally DA denervated animal wasunable to orient towards any sensory stimuli applied to the side of the body that is contralateral to the lesion while it reacts normally to all stimuli applied to the side ipsilateral to the lesion. In connection with the postulated involvement of the central DA pathways in “extrapyramidal” motor control it may be argued that the lack of orienting reaction is due to motor disability. However, the time course of recovery differs among the different sensory modalities and at a given time point the animal may react to certain sensory stimuli while not to others indicating that there is no non-specific motor disability preventing him from performing the orienting response. These deficits in responding to sensory stimuli after lesions of the DA neurons are also evident in a more complex situation e.g. running a maze to get water reward. Bilateral removal of the ascending DA neurons induces serious akinesia, adipsia and aphagia and abolishes the ability to perform an already well trained response. If the degeneration of the DA neurons is the cause of this disruption of learned behaviour it should be possible to restore the behaviour by compensating for the lost DA with e.g. the DA precursor Dopa or the DA receptor stimulating drug apomorphine. In fact, both these drugs are able to