Discover the neural circuits and molecular mechanisms that mediate the reinforcing and pleasurable subjective effects of alcohol and other drugs
Identify the long-term effects of cocaine and alcohol abuse during adolescence
Identify novel neural targets and validate pharmacological compounds that may be used to treat problems associated with alcohol and drug abuse
Research Synopsis:
Our studies have shown that the limbic system and extended amygdala regulate alcohol-seeking behavior and conditioned discriminative stimulus effects of alcohol. We established that neuropeptide-Y in the hypothalamus modulates excessive alcohol drinking similar to its role in obesity via the Y1 receptor, and that NPY-Y5 receptor blockade reduces the reinforcing effects of alcohol. Also, using gene knockout mice, we have shown that Protein Kinase C-ε regulates alcohol drinking, reinforcement, sensitivity, withdrawal, and mesolimbic dopamine release through enhancement of GABA-A receptor function. Other studies have shown that adolescent exposure to cocaine leads to enhanced vulnerability to the rewarding effects of cocaine during adulthood in mice via activation of the limbic system.
Recent Publications:
Hodge, C.W., Miles, M.F., Sharko, A.C., Stevenson, R.A., Hillmann, J.R., Lepoutre, V., Besheer, J., and Schroeder, J.P. (2006) The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Psychopharmacology (Berl) 183(4): 429-38. Abstract
Schroeder JP, Overstreet DH, and Hodge CW. (2005) The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats. Psychopharmacology (Berl) 179(1): 262-70. Abstract
Besheer, J., and Hodge, C.W. (2005) Pharmacological and anatomical evidence for an interaction between mGluR5- and GABA(A) alpha1-containing receptors in the discriminative stimulus effects of ethanol. Neuropsychopharmacology. 30(4): 747-57. Abstract
Olive, M.F., McGeehan, A.J., Kinder, J.R., McMahon, T., Hodge, C.W., Janak, P.H., and Messing, R.O. (2005) The mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine decreases ethanol consumption via a protein kinase C epsilon-dependent mechanism. Mol Pharmacol 67(2): 349-55. Abstract
Camarini, R., and Hodge, C.W. (2004) Ethanol preexposure increases ethanol self-administration in C57BL/6J and DBA/2J mice. Pharmacol Biochem Behav 79(4): 623-32. Abstract
