Desipramine enhances the ability of risperidone to decrease alcohol intake in the Syrian golden hamster

The atypical antipsychotic clozapine reduces alcohol drinking in patients with schizophrenia. We have proposed that clozapine׳s ability to decrease alcohol drinking relates to its weak blockade of the dopamine D2 receptor and potent blockade of the norepinephrine α-2 receptor, as well as its ability to elevate plasma and brain norepinephrine. Another atypical antipsychotic, risperidone, which is a potent blocker of both the dopamine D2 receptor and norepinephrine α-2 receptor, does not decrease alcohol drinking. In this study, we used the Syrian golden hamster to test whether the ability of risperidone to reduce alcohol drinking would be enhanced if it was used in combination with the norepinephrine reuptake inhibitor desipramine. Hamsters were given free access to water and alcohol (15% v/v) until they reached a steady drinking baseline. They were then treated daily with each drug or drug combination for 20 days. Risperidone (0.2mg/kg) only transiently decreased alcohol drinking. However, 5.0mg/kg, and possibly 1.0mg/kg, desipramine added to 0.2mg/kg risperidone appeared to produce a more substantial and relatively sustained effect than risperidone alone. Data from this study provide leads toward the development of new treatments for patients with schizophrenia and alcoholism, and also for those with alcoholism alone.