Microdialysis Studies of Self-administrationx

Wise, Roy A.

Abstract

The habit-forming effects of several addictive drugs have been linked to their ability to elevate levels of the neurotransmitter dopamine in certain brain regions. It is important to determine which other neurotransmitters control the dopamine system and which transmitter systems dopamine controls. Two types of microdialysis studies are employed to identify neurotransmitter fluctuations that accompany drug-seeking behavior or that cause or are caused by fluctuations of dopamine. In the first, microdialysis samples are taken from various brain regions in animals trained to lever-press for intravenous drug injections. In the other, portions of drug-associated brain circuitry are stimulated and subsequent neurotransmitter fluctuations are determined from microdialysis samples distant from the site of stimulation. The results of these studies are integrated identify the neuronal circuitry of addiction and drug-seeking. Our most recent finding is that the excitatory neurotransmitter glutamate brings information about reward-associated conditioned stimuli to the dopamine system that responds directly to cocaine.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Drug Abuse (NIDA)
• Type: Intramural Research (Z01)
• Project #: 1Z01DA000471-04
• Application #: 7593280
• Support Year: 4
• Fiscal Year: 2007
• Total Cost: $2,932,169

Institution

• Name: National Institute on Drug Abuse
• Country: United States

Publications

Steidl, S; Myal, S; Wise, R A (2015) Supplemental morphine infusion into the posterior ventral tegmentum extends the satiating effects of self-administered intravenous heroin. Pharmacol Biochem Behav 134:1-5

Hope, Bruce T; Nagarkar, Deepti; Leonard, Sherry et al. (2007) Long-term upregulation of protein kinase A and adenylate cyclase levels in human smokers. J Neurosci 27:1964-72

Wang, Bin; You, Zhi-Bing; Rice, Kenner C et al. (2007) Stress-induced relapse to cocaine seeking: roles for the CRF(2) receptor and CRF-binding protein in the ventral tegmental area of the rat. Psychopharmacology (Berl) 193:283-94

You, Zhi-Bing; Wang, Bin; Zitzman, Dawnya et al. (2007) A role for conditioned ventral tegmental glutamate release in cocaine seeking. J Neurosci 27:10546-55

Quarta, Davide; Ciruela, Francisco; Patkar, Kshitij et al. (2007) Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release. Neuropsychopharmacology 32:35-42

Wise, Roy A (2006) The parsing of food reward. Am J Physiol Regul Integr Comp Physiol 291:R1234-5

Zangen, Abraham; Solinas, Marcello; Ikemoto, Satoshi et al. (2006) Two brain sites for cannabinoid reward. J Neurosci 26:4901-7

Wise, Roy A (2006) A new peptide input to learning and addiction. Neuron 49:483-4

Wise, Roy A (2006) Role of brain dopamine in food reward and reinforcement. Philos Trans R Soc Lond B Biol Sci 361:1149-58

Hope, B T; Crombag, H S; Jedynak, J P et al. (2005) Neuroadaptations of total levels of adenylate cyclase, protein kinase A, tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area do not correlate with expression of sensitized or tolerant locomotor responses to co J Neurochem 92:536-45