Animal Models of Addiction and Neuropsychiatric Disorders and Their Role in Drug Discovery: Honoring the Legacy of Athina Markou.

Each of the co-authors worked with Athina Markou, at different stages of our careers and in different capacities, to develop, optimize, and use animal models of drug addiction and, more generally, mental health disorders such as anxiety, depression, and schizophrenia. Here, we briefly summarize some of our work with Athina, primarily involving the use of the intracranial self-stimulation and intravenous drug self-administration procedures. This work established that excessive consumption of addictive drugs can induce profound dysfunction in brain reward circuits. Such drug-induced reward deficits are likely to play a key role in precipitating the emergence of compulsive drug-seeking behaviors. We also summarize findings suggesting that perturbations in glutamatergic transmission contribute to brain reward deficits in drug-dependent animals and that metabotropic glutamate receptors are potential targets for the development of novel medications to facilitate long-term drug abstinence and prevention of relapse.