Influence of morphine self-administration on gene expression in the rat amygdala was studied using rat genome DNA arrays U34A from Affymetrix. Animals were trained to self-administer morphine, each having two 'yoked' control animals, receiving passive injections of either morphine or saline. After 40 sessions of self-administration, amygdalae were removed, total RNA was isolated and used to prepare probes for Genechip Ò arrays. The treatment was found to significantly change abundance of 29 transcripts. Analysis by means of reverse transcription real-time PCR showed significant changes in abundance of five transcripts: c protein kinase C (PKC), upstream binding factor 2 (UBF2), lysozyme, noggin and heat shock protein 70 (hsp70). After 30 days of forced abstinence from morphine self-administration, abundance of hsp70 and lysozyme returned to basal levels. Changes in abundance of UBF2 persisted, and abundance of three additional genes, namely nuclear factor I/A, c 1 subunit of GABA A receptor and the neuronal calcium sensor 1, changed. Additionally, acute as well as chronic intraperitoneal morphine administration changed the abundance of PKC c, c 1 subunit of GABA A and hsp70 genes. Keywords: addiction, amygdala, DNA arrays, morphine selfadministration.Addiction, a persistent state in which compulsive drug use escapes control, is the most serious consequence of repetitive drug taking. Although the number of known drugs that produce dependence is increasing, little is known regarding cellular and molecular mechanisms of addiction. It is believed that the development of addiction is associated with plastic changes and long-term potentiation in discrete parts of the central nervous system (Nestler 2001). Nevertheless, molecular changes in gene expression underlying these phenomena are still poorly understood.Brain regions involved in reinforcing drug effects, development of addiction and drug craving comprise the mesocorticostriatal areas and the so-called extended amygdala (Alheid and Heimer 1988;Kreek and Koob 1998). The best known targets for drugs of abuse are the dopaminergic neurones that project from the ventral tegmental area of the midbrain to the nucleus accumbens, as well as to other forebrain sites, including amygdala. The amygdala has been characterized as a relay station between the input of emotionally significant stimuli and the output of behavioural responses (Dent et al. 2001). It processes an information about the emotional and motivational significance of environmental stimuli (Everitt et al. 1991;McDonald 1991;Hatfield et al. 1996). Animal models of drug craving and relapse are based largely on conditioned reinforcement. The neural substrates for such conditioned positive reinforcement appear to involve parts of the extended amygdala and afferent pathways from the basolateral amygdala (Everitt et al. 1991). Thus, the amygdala is implicated in conditioned reinforcement and may play a crucial role in conditioned and emotional aspects of addiction. Received December 8, 2003; revised manuscri...
The expression of the Calcium/Calmodulin-Dependent Protein Kinase I gamma (encoded by the Camk1g gene) depends on the activation of glucocorticoid receptors (GR) and is strongly regulated by stress. Since Camk1g is primarily expressed in neuronal cells of the limbic system in the brain, we hypothesized that it could be involved in signaling mechanisms that underlie the adaptive or maladaptive responses to stress. Here, we find that restraint-induced stress and the GR agonist dexamethasone robustly increase the expression of Camk1g in neurons of the amygdalar nuclei in the mouse brain. To assess the functional role of Camk1g expression, we performed a virally induced knock-down of the transcript. Mice with bilateral amygdala-specific Camk1g knock-down showed increased anxiety-like behaviors in the light-dark box, and an increase in freezing behavior after fear-conditioning, but normal spatial working memory during exploration of a Y-maze. Thus, we confirm that Camk1g is a neuron-specific GR-regulated transcript, and show that it is specifically involved in behaviors related to anxiety, as well as responses conditioned by aversive stimuli.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.