Dopamine transporter mutants, small molecules, and approaches to cocaine antagonist/dopamine transporter disinhibitor development.
1998
Publisher Summary
Dopamine transporters(DAT) terminate dopaminergic
neurotransmissionby Na + and Cl − dependent reaccumulation of
dopamineinto presynaptic neurons. A number of substantial lines of evidence have suggested that the actions of cocaine in inducing its rewarding and reinforcing properties are largely because of its inhibition of the DAT, especially the transporter expressed on terminals of mesolimbic-mesocortical dopaminergic neurons whose cell bodies lie in the
ventral tegmental area(VTA) of the basal midbrain. Reduction in psychostimulant reward after lesions of these VTA neurons, the ability of psychostimulants to enhance
dopaminespillover from their terminal areas in
nucleus accumbens, the good correlations between the relative potencies of cocaine analogs in tests of behavioral reward and their potencies at the
dopamine transporter, and results in transgenic animals in which
dopamine transporteris overexpressed in
catecholaminergicneurons or deleted—have been interpreted as fitting with the idea that the role of cocaine in reward largely depend on its action at the
dopamine transporter. Thus, the chapter explains
dopamine transportermutants, small molecules, and approaches to cocaine antagonist and
dopamine transporterdisinhibitor development.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
24
References
21
Citations
NaN
KQI