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Although the alteration in brain information processing that leads to drug abuse and addiction is incompletely understood, changes in dopamine neuron excitability appear to play an important role in these processes.Â Ongoing research projects are seeking Â to identify the long-term consequences of stress on the dopamine neuron excitability and the impact of those changes on the addictive qualities of drugs of abuse, and the development of novel therapeutic approaches for treating PTSD and PTSD-related addictions
We approach the problem of drug-dopaminergic interactions by using a variety of neuropharmacologic and electrophysiological techniques. Toward this aim extracellular recordings are performed in the anesthetized animal under various drug treatment designs. Extra- and Intracellular recordings from dopamine neurons in brain slice preparations have also been used to examine the interaction of drugs and specific neurotransmitters on activity and ion conductance mechanisms in these neurons. Small quantities of drugs can also be applied directly onto single nerve cells for mechanistic studies of drug action. In addition, the use of techniques to eliminate or deplete essential transmitter substances in whole animals are often combined with behavioral measures designed to assess the potential role of various anatomical/transmitter inputs onto these dopamine neurons. Current studies also utilize transgenic mice with null mutation of specific nicotinic receptor subunits.
Riegel AC, Ali SF, French ED (2003) Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268. Neuropsychopharmacol 28:1440-1447.
Riegel A, French ED (2002) Abused inhalants and central reward pathways: Electrophysiological and behavioral studies in the rat. Ann N Y Acad Sci 965:1-11.
Wu X, French ED (2000) Effects of chronic delta-9-tetrahydrocannabinol on rat midbrain dopamine neurons: An electrophysiological assessment. Neuropharmacol 39:391-398.
Yin R, French ED (2000) A comparison of the effects of nicotine on dopamine and non-dopamine neurons in the rat ventral tegmental area: an in vitro electrophysiological study. Brain Res Bulletin 51:507-514.
The abused inhalant toluene increases dopamine release in the nucleus accumbens by directly stimulating ventral tegmental area neurons, by A.C.Riegel, A. Zapata, T.S. Shippenberg, and E.D. French, in Neuropsychopharmacology, 2006.