Christopher V Dayas
University of Newcastle, Australia
Dr. Dayas completed his PhD at the University of Queensland (2001). The focus of his doctoral studies was the study of brain pathways that control hormonal responses to stress. In 2003 he received a prestigious National Health & Medical Research Council of Australia (NHMRC) CJ Martin Fellowship and carried out post-doctoral training at the Scripps Research Institute, San Diego, USA. He has published numerous papers on the role of the hypothalamus in controlling stress responses or drug-motivated behaviours. In 2008, he received an NHMRC New Investigator Grant and is currently a Senior Lecturer in the School of Biomedical Sciences and Pharmacy, and Deputy Director of the Centre for Brain and Mental Health Research, University of Newcastle, NSW, Australia.
The neuropeptides orexins (hypocretins) and cocaine and amphetamine-regulated transcript (CART) have been identified as potential targets for developing pharmacotherapies to treat drug relapse. Our group has recently focused on the paraventricular thalamus (PVT) - part of the dorsal midline and intralaminar thalamic group – as a possible key site in the integration of orexin (OrX) and CART signaling. We have also begun to investigate whether drug-induced plasticity occurs at the level of the hypothalamus and may affect the recruitment of hypothalamic neurons by drug cues or stress. We have found that intra-PVT injections of the active CART55-102 peptide, negatively modulates cocaine-seeking behavior. However, the OrX-1 receptor antagonist SB-334867 injected into the PVT failed to alter drug-seeking behavior. Because of electrophysiological evidence indicating that orexins modulate dopamine neuron activity in the ventral tegmental area (VTA), we tested the effect of intra-VTA SB-334867 on relapse-like behavior. Intra-VTA SB-334867 significantly suppressed cocaine-seeking but failed to alter natural reward-seeking or locomotor behavior. With regards to drug-induced hypothalamic plasticity, we found that cocaine promotes an increase in excitatory (vesicular glutamate transporter 2)-positive inputs, but not inhibitory inputs, that are closely opposed to orexin neurons. These anatomical changes were supported by electrophysiological recordings in hypothalamic slices showing that passive or self-administered cocaine increased the frequency but not amplitude of excitatory post-synaptic currents in putative orexin-positive neurons. Together these studies have significantly increased out understanding of the brain circuitry that controls drug-seeking and have provided insight into approaches to reduce drug-seeking by targeting aberrant hypothalamic peptide signaling.