[Dopamine control of neuroendocrine functions. New findings based on the study of transgenic animals].
The dopamine system is implicated in the control of locomotion, cognition and endocrine function. The relative contribution of the various dopamine related components is not well established mainly because drugs that target the dopaminergic system often lack selectivity. The gene inactivation procedure in vivo, or knock out, permits the creation of new strains of mice specifically lacking a designated gene. Unlike pharmacological approaches this molecular procedure offers a unique specificity for the target gene. This technique has been applied recently to inactivate the expression of tyrosine hydroxylase, dopamine, monoamine oxidase, three of the five dopamine receptors, the monoamines vesicular transporter and the plasma membrane dopamine transporter. Here we summarize the main findings obtained with these transgenic animals carrying these "genetic defects" leading to a better understanding of the relative contribution of each of the corresponding gene product regarding locomotor activity, regulation of the expression of peptides under the dopamine control, responses to various drugs targeting the dopamine system and control of pituitary function. A special emphasis is made on the consequences of the knock out of the dopamine transporter where our results establish not only the central importance of the transporter as the key element controlling DA levels in the brain and pituitary, but also its role as an obligatory target for the behavioral and biochemical action of amphetamine and cocaine. Besides the better comprehension of the dopamine transmission, these strains of mice offer unique models to test the specificity and selectivity of dopamine acting drugs and have often provided key elements leading to possible clinical and social implications for illnesses such as Parkinson disease, dwarfism and drug addiction.
Jaber
M
M
CNRS UMR 5541, Université de Bordeaux II.
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008124:Locomotion / Q000502:physiology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D009490:Neurosecretory Systems / Q000502:physiology*
D000662:Amphetamines; D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D003042:Cocaine; D004298:Dopamine