Drugs of abuse are thought to have the common action of increasing dopaminergie transmission in the mesolimbic dopamine (DA) pathway, specifically in the nucleus accumbens (NAc). However, sedative-hypnotics, including the barbiturates, are anomalous in that they appear to stimulate DA release from the NAc at doses that are generally lower than their reinforcing doses. The fact that barbiturates have a long history of abuse in humans and are potent reinforcers in laboratory animals, but are behaviourally reinforcing only at doses that decrease DA release from the NAc, raises questions about the neuropharmacological mechanism of reinforcement in these drugs. Indeed, of the numerous studies that have examined the reinforcing properties of barbiturates, none have examined the pharmacological basis of their reinforcing effects. / The conditioned place preference (CPP) paradigm is a widely used behavioural test that assesses the reinforcing capacity of stimuli by the ability of conditioned stimuli to evoke an approach response. Using this paradigm, systemic administration of pentobarbital (15 mg/kg) induced a significant place preference. Furthermore, pretreatment with GABAA, DA, and opioid receptor antagonists blocked the pentobarbital-induced place preference. Sodium barbital, a longer-acting barbiturate also induced a significant CPP when systemically administered (8 and 24 mg/kg). Moreover, the reinforcing effect of this place preference is centrally mediated, assessed by the significant CPP obtained with intracerebroventricular (ICV) injections of barbital (240 and 480 mug). / A number of different brain sites are involved in the reinforcing effects of drugs of abuse. Microinjections of barbital into the periaqueductal gray (25 mug) or posterior ventral tegmental area (VTA; 15 mug), but not into other areas, such as the amygdala and anterior VTA, produced a place preference. Furthermore, opioid (naloxone methiodide) and GABAA receptor (SR 95531) antagonists administered into these areas blocked the ICV barbital place preference. Given these findings, barbiturate reinforcement appears to be mediated by the same neural substrates and neurochemical systems as other drugs of abuse, such as opiates and ethanol. The implications of these results and the use of barbital in the place preference paradigm to investigate the neuropharmacological mechanisms of barbiturate reinforcement are discussed.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82833 |
| Date | January 2002 |
| Creators | Bossert, Jennifer Marie |
| Contributors | Franklin, Keith B. J. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Psychology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001984080, proquestno: AAINQ88426, Theses scanned by UMI/ProQuest. |
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