 |
 |
Faculty
Loren Parsons
Associate Professor
Committee On The Neurobiology Of Addictive Disorders
TSRI - 1992
Education
Ph.D., Emory University, 1992
Research Focus
Neurochemistry of Addiction: Serotonin and Endocannabinoid Neurotransmission
Work in our laboratory is focussed on elucidating the neurochemical mechanisms that contribute to the induction and maintenance of drug dependence, with specific regard to central serotonin and endogenous cannabinoid neurotransmission. Most recently we have been studying the involvement of central serotonin-1B (5-HT1B), and cannabinoid-1 (CB1) receptors in the modulation of cocaine, ethanol and opiate self-administration. Our approach is to employ in vivo microdialysis to follow extracellular neurochemical events both during drug self-administration and after pharmacological manipulations. Pharmacological manipulations of behavior are often utilized as a complementary approach. Our data suggest that central 5-HT1B receptors provide a facilitory influence on the reinforcing effects produced by both cocaine and ethanol. 5-HT1B receptors in both the ventral tegmental area and nucleus accumbens have been implicated this process. The mechanism for this modulation of drug reward involves the regulation of mesolimbic dopamine neurotransmission, and 5-HT1B receptors exert their effect on this system by altering the release of both excitatory and inhibitory amino acid neurotransmitters. Extended exposure to cocaine induces a downregulation of 5-HT1B effects in the ventral tegmental area, but not nucleus accumbens, suggesting that long-term cocaine exposure disrupts the balance of 5-HT1B mechanisms. Current experiments are designed to determine whether this 5-HT1B receptor dysfunction contributes to the induction and maintenance of dependence. We have also found that CB1 receptor blockade alters the self-administration of heroin and ethanol, but not cocaine. The mechanism for these effects is unknown, but at present does not appear to involve alterations in mesolimbic dopamine neurotransmission.
Selected References
Frantz, K.J., Hansson, K.J., Stouffer, D.G., Parsons, L.H. 5-HT6 receptor antagonism potentiates the behavioral and neurochemical effects of amphetamine but not cocaine. Neuropharmacology 42:170-180, 2002.
Parsons, L.H., Kerr, T.M., Tecott, L.H. 5-HT1A receptor mutant mice exhibit enhanced tonic, stress-induced and fluoxetine-induced serotonergic neurotransmission. J. Neurochem. 77:607-617, 2001.
Parsons, L.H., Weiss, F. Koob, G.F. Serotonin1B receptor stimulation enhances cocaine reinforcement. J. Neurosci. 18:10078-10089, 1998.
Giuffrida, A., Parsons, L.H., Kerr, T.M., Rodriguez de Fonseca, F., Navarro, M., Piomelli D. Dopamine activation of endogenous cannabinoid signalling in dorsal striatum. Nature Neurosci. 2:358-363, 1999.
|
|
