(Download) "Anatomy and Pharmacology of Dopamine Transporter-Mediated Reward and Locomotor Responses to Psychostimulants" by Brian O'Neill # eBook PDF Kindle ePub Free

📘 Read Now     📥 Download

eBook details

• Title: Anatomy and Pharmacology of Dopamine Transporter-Mediated Reward and Locomotor Responses to Psychostimulants
• Author : Brian O'Neill
• Release Date : January 19, 2013
• Genre: Psychology,Books,Health, Mind & Body,Spirituality,Science & Nature,
• Pages : * pages
• Size : 10179 KB

Description

Psychostimulants are addictive drugs that exert their effects mainly through inhibition of the dopamine, norepinephrine, and serotonin transporter reuptake activities. Previous studies have shown that dopamine transporter (DAT) blockade is necessary for expression of cocaine-induced reward and locomotor behaviors – both of which are potentially upstream of the development of addiction. However, there is little neuroanatomical specificity in many of these studies, and it is unclear how the norepinephrine (NE) and serotonin (5-HT) systems may contribute to the development of addiction. We hypothesized that DAT in the dorsal and ventral striatum are important targets for cocaine-induced hyperlocomotion and reward, respectively. We also hypothesized that NET and SERT inhibition play a modulatory role in these behaviors. Therefore in these studies, the effects of DAT inhibition are studied in a brain region-specific manner and the contribution of the NE and 5-HT systems are probed either directly or indirectly. In the first experiments (chapter 2), the anatomical questions are investigated by using viral vectors for restoration of the wild-type DAT gene to certain brain regions of a cocaine-insensitive, mutant DAT knock-in mouse (DAT-CI mice). From this, we found that DAT blockade in the rostrolateral striatum is involved in cocaine-induced locomotion, but not reward. We did not find a discrete brain region where the viral injection restored cocaine-induced reward behaviors. For the second set of experiments, we show that blockade of non-DAT targets, such as the norepinephrine transporter (NET) and/or the serotonin transporter (SERT), are sufficient for inducing cocaine conditioned place aversion (chapter 3). We also show that the genetic background of DAT-CI mice is critical in determining whether or not cocaine is aversive – and whether amphetamine is a stimulant of locomotion (chapter 4) – effects that are generally thought to be compulsory. Several projects that yielded few or equivocal results, regarding also the contribution of non-DAT targets, will be presented briefly (chapter 5). In summary of the findings, the anatomical experiments show that DAT-inhibition in the rostrolateral striatum is involved in cocaine-induced hyperlocomotion. They also show that DAT-inhibition in the dorsal striatum, or the ventral striatum are effectively insufficient to produce either cocaine-induced reward or hyperlocomotion. The second set of experiments highlight the importance of genetic background in the modulation of reward and locomotor behaviors – even in inbred mouse models – as well as the involvement of non-DAT targets in aversive behaviors that counteract reward. These results bring us closer to understanding the interaction of reward and motor-related brain regions in addiction, as well as to understanding the genetic and neurochemical origins of their outputs.

Books Free Download "Anatomy and Pharmacology of Dopamine Transporter-Mediated Reward and Locomotor Responses to Psychostimulants" PDF ePub Kindle