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Changes in dopamine transporter and c-Fos expression in the nucleus accumbens of alcohol-tolerant rats.
Alcohol Clin Exp Res. 2000 Mar; 24(3):361-5.AC

Abstract

BACKGROUND

We have shown that neurochemical functions of 5-HT3 receptors in regulating dopamine (DA) release in the nucleus accumbens (ACC) after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance, and that the development of alcohol dependence may be mediated by ACC 5-HT3 receptors. In the present study, the effects of chronic alcohol consumption on the functions of the dopamine transporter (DAT) and the expression of c-Fos proteins were investigated using in vivo brain microdialysis and immunocytochemistry.

METHODS

Perfusion of cocaine and 1-(2-Bis-(4-fluorophenyl) methoxy) ethyl)-4-(3-phenylpropyl) piperizine (GBR 12909) through the microdialysis probe membrane increased the extracellular levels of DA in ACC of alcohol-treated rats that had developed alcohol tolerance by drinking 10% EtOH for 30 days.

RESULTS

The magnitudes of DA reuptake or DAT inhibitors, cocaine, and GBR 12909 that induced DA availability in the ACC were significantly higher in alcohol-treated rats than in controls. When compared with control rats, the alcohol-treated rats exhibited higher levels of DA and its metabolite, DOPAC, in the ACC. Increased expression of the c-Fos-like protein was found in the ACC of alcohol-treated rats. These results show that (1) chronic alcohol consumption desensitizes or decreases the DAT of DA terminals in the ACC and that (2) EtOH causes cellular hyperexcitability of ACC dopaminergic neurons with increased Fos expression during alcohol tolerance.

CONCLUSION

The findings suggested that an abnormality of the dopaminergic neurons in the ACC that are involved with DAT dysfunction is associated with the development of alcohol tolerance.

Authors+Show Affiliations

Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan. kyoshimo@basic.kpu-m.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10776677

Citation

Yoshimoto, K, et al. "Changes in Dopamine Transporter and c-Fos Expression in the Nucleus Accumbens of Alcohol-tolerant Rats." Alcoholism, Clinical and Experimental Research, vol. 24, no. 3, 2000, pp. 361-5.
Yoshimoto K, Ueda S, Nishi M, et al. Changes in dopamine transporter and c-Fos expression in the nucleus accumbens of alcohol-tolerant rats. Alcohol Clin Exp Res. 2000;24(3):361-5.
Yoshimoto, K., Ueda, S., Nishi, M., Yang, Y., Matsushita, H., Takeuchi, Y., Kato, B., Kawai, Y., Noritake, K., Kaneda, S., Sorimachi, Y., & Yasuhara, M. (2000). Changes in dopamine transporter and c-Fos expression in the nucleus accumbens of alcohol-tolerant rats. Alcoholism, Clinical and Experimental Research, 24(3), 361-5.
Yoshimoto K, et al. Changes in Dopamine Transporter and c-Fos Expression in the Nucleus Accumbens of Alcohol-tolerant Rats. Alcohol Clin Exp Res. 2000;24(3):361-5. PubMed PMID: 10776677.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in dopamine transporter and c-Fos expression in the nucleus accumbens of alcohol-tolerant rats. AU - Yoshimoto,K, AU - Ueda,S, AU - Nishi,M, AU - Yang,Y, AU - Matsushita,H, AU - Takeuchi,Y, AU - Kato,B, AU - Kawai,Y, AU - Noritake,K, AU - Kaneda,S, AU - Sorimachi,Y, AU - Yasuhara,M, PY - 2000/4/25/pubmed PY - 2000/6/17/medline PY - 2000/4/25/entrez SP - 361 EP - 5 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 24 IS - 3 N2 - BACKGROUND: We have shown that neurochemical functions of 5-HT3 receptors in regulating dopamine (DA) release in the nucleus accumbens (ACC) after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance, and that the development of alcohol dependence may be mediated by ACC 5-HT3 receptors. In the present study, the effects of chronic alcohol consumption on the functions of the dopamine transporter (DAT) and the expression of c-Fos proteins were investigated using in vivo brain microdialysis and immunocytochemistry. METHODS: Perfusion of cocaine and 1-(2-Bis-(4-fluorophenyl) methoxy) ethyl)-4-(3-phenylpropyl) piperizine (GBR 12909) through the microdialysis probe membrane increased the extracellular levels of DA in ACC of alcohol-treated rats that had developed alcohol tolerance by drinking 10% EtOH for 30 days. RESULTS: The magnitudes of DA reuptake or DAT inhibitors, cocaine, and GBR 12909 that induced DA availability in the ACC were significantly higher in alcohol-treated rats than in controls. When compared with control rats, the alcohol-treated rats exhibited higher levels of DA and its metabolite, DOPAC, in the ACC. Increased expression of the c-Fos-like protein was found in the ACC of alcohol-treated rats. These results show that (1) chronic alcohol consumption desensitizes or decreases the DAT of DA terminals in the ACC and that (2) EtOH causes cellular hyperexcitability of ACC dopaminergic neurons with increased Fos expression during alcohol tolerance. CONCLUSION: The findings suggested that an abnormality of the dopaminergic neurons in the ACC that are involved with DAT dysfunction is associated with the development of alcohol tolerance. SN - 0145-6008 UR - https://www.unboundmedicine.com/medline/citation/10776677/Changes_in_dopamine_transporter_and_c_Fos_expression_in_the_nucleus_accumbens_of_alcohol_tolerant_rats_ DB - PRIME DP - Unbound Medicine ER -