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Effects of 3,4-methylenedioxymethamphetamine (MDMA) on Cholinergic neurons in the rat brain

Nair, Sunila
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123857787

Abstract Details

2005, PhD, University of Cincinnati, Pharmacy : Pharmaceutical Sciences.
3,4-Methylenedioxymethamphetamine (MDMA), an amphetamine analog, is a psychomotor stimulant and a popular drug of abuse. The effect of MDMA on the release of the monoamine neurotransmitters serotonin (5-HT) and dopamine (DA) has been well documented. In contrast, very little is known about the influence of MDMA on other neurotransmitter systems. In view of feelings of heightened awareness and behavioral arousal in human MDMA users, and the role of the cholinergic system in processing environmental cues following novel and arousing stimuli, the influence of MDMA on acetylcholine (ACh) release was examined in the prefrontal cortex (PFC) and hippocampus. Using in vivo microdialysis, it was determined that MDMA enhances the release of ACh in the PFC and hippocampus, possibly by mechanisms localized to these brain regions. In addition, it was also determined that MDMA-induced release of ACh in the PFC, but not hippocampus, is mediated by serotonergic and dopaminergic mechanisms. Further studies examining the role of various 5-HT and DA receptors in the MDMA-induced release of ACh in the PFC indicate that receptors of the 5-HT4 and D1 subtype mediate the release of cortical ACh induced by MDMA. Whereas MDMA use has been associated with behavioral activation and cortical arousal immediately following drug intake, in the long term the drug is known to produce significant cognitive impairments. In view of the cognitive impairments following MDMA use and administration, and the central role of ACh in attentional processing and cognition, studies were designed to assess the influence of a neurotoxic regimen of MDMA, on the subsequent stimulation of ACh release in the PFC. Prior treatment with a 5-HT depleting regimen of MDMA resulted in decreased ACh release in response to subsequent administration of MDMA. In contrast, treatment with a neurotoxic regimen of MDMA did not significantly alter the subsequent stimulation of ACh release induced by application of tail pinch or by the novelty of an intruder rat. Thus, results from the present study indicate that although a 5-HT depleting regimen appears to inhibit subsequent MDMA-induced ACh release in the PFC, it has little impact on subsequent stimulation of ACh release by physiological stressors.
Dr. Gary Gudelsky (Advisor)
215 p.
Health Sciences, Pharmacology

Recommended Citations

Citations

  • Nair, S. (2005). Effects of 3,4-methylenedioxymethamphetamine (MDMA) on Cholinergic neurons in the rat brain [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123857787

    APA Style (7th edition)

  • Nair, Sunila. Effects of 3,4-methylenedioxymethamphetamine (MDMA) on Cholinergic neurons in the rat brain. 2005. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123857787.

    MLA Style (8th edition)

  • Nair, Sunila. "Effects of 3,4-methylenedioxymethamphetamine (MDMA) on Cholinergic neurons in the rat brain." Doctoral dissertation, University of Cincinnati, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123857787

    Chicago Manual of Style (17th edition)

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© 2005, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.