PMID: 8959023Oct 31, 1996Paper

A genetic approach to study mechanisms of cocaine action

Annals of the New York Academy of Sciences
M XuS Tonegawa

Abstract

The brain dopamine system is thought to be the major target for the neuropharmacological actions of psychomotor stimulants such as cocaine. To investigate the mechanisms of cocaine action, we used a genetic approach, the gene-targeting technique, and generated D1 dopamine receptor mutant mice. Locomotor activity analysis in response to cocaine indicates that, in contrast to control mice which showed a dose-dependent increase in locomotion, D1 receptor mutant mice exhibited a dose-dependent decrease, suggesting that D1 receptors play an essential role in mediating such effects. Extracellular single unit recording of dopamine sensitive nucleus accumbens neurons in the D1 receptor mutant mice and control mice revealed a marked reduction in the inhibitory effects of cocaine and dopamine on the generation of action potentials, suggesting that D1 receptors play a fundamental role in cocaine- and dopamine-mediated neurophysiological effects within the nucleus accumbens. From these analyses, we conclude that the D1 dopamine receptor plays essential roles in mediating these effects of cocaine. In the future, the use of this powerful genetic approach will be essential for elucidating the molecular components of the signal transduction pa...Continue Reading

References

Jan 11, 1979·Nature·J W Kebabian, D B Calne
May 1, 1992·Trends in Pharmacological Sciences·G F Koob
Aug 1, 1991·Pharmacology, Biochemistry, and Behavior·D R BrittonD Kerkman
Jul 1, 1991·Trends in Neurosciences·M J KuharJ W Boja
Jan 1, 1991·Physiological Reviews·M Le Moal, H Simon
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A M GraybielH A Robertson
Jan 1, 1989·Neuroscience and Biobehavioral Reviews·T W RobbinsB J Everitt
Jun 1, 1989·Pharmacology, Biochemistry, and Behavior·D M Wood, M W Emmett-Oglesby
Nov 4, 1988·Science·G F Koob, F E Bloom
Jan 1, 1983·Progress in Neuro-psychopharmacology & Biological Psychiatry·A G PhillipsH C Fibiger
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·P A FurthL Hennighausen
Sep 1, 1993·Brain Research. Brain Research Reviews·T E Robinson, K C Berridge
May 1, 1993·Pharmacology, Biochemistry, and Behavior·R MaldonadoG F Koob
Jan 1, 1990·Behavioural Pharmacology·F.J. White
Jan 1, 1990·Behavioural Pharmacology·J. BergmanR.D. Spealman

❮ Previous
Next ❯