Role of Teneurin C-Terminal Associated Peptides in the Stress-Induced Reinstatement of Cocaine Seeking
Corticotropin-releasing factor (CRF) is a chemical found naturally in the brain that plays a key role in the stress response. CRF is also known to be involved in anxiety and mood disorders, as well as various aspects of drug dependence, including long-term relapse to drug use. Pathological symptoms in the form of mood disorders and substance abuse occur, at least in part, as a result of aberrant activity within CRF systems. From this perspective, CRF is a logical target for drug development in the treatment of these disorders. The recently discovered teneurin C-terminal associated peptides (TCAP) comprise a chemical system in the brain that naturally regulates CRF activity. More specifically, TCAP is believed to have inhibitory effects on CRF and may, thereby, have important therapeutic implications in the treatment of mood and substance abuse disorders. The present work will be carried out to determine whether TCAP administration can, specifically, interfere in the effects of stress on relapse to cocaine use, an effect that is known to be mediated by CRF. In a first set of experiments, an animal model of relapse, known as the reinstatement procedure, will be used to study how exposure to TCAP affects the ability of stressors to reinstate cocaine-seeking behavior in rats. A second set of experiments will explore how exposure to TCAP alters brain activity in response to those stressors. Overall, it is expected that this work will help to establish the potential of TCAP as a target for the treatment of drug relapse and, thereby, extend the initiatives of PTI to a characterization of the role of TCAP-CRF interactions in drug dependence.