[Behavioral and pharmacological characteristics of mice lacking the dopamine transporter].
Dopamine exerts an important modulatory influence on behaviors such as emotions and locomotor activity. The dopamine transporter (DAT) reuptakes the released neurotransmitter into presynaptic terminals. Mice lacking the dopamine transporter (DAT knock-out mice) display marked changes in an dopamine homeostasis that result in an elevated dopaminergic level and locomotor hyperactivity. The interaction of psychostimulating drugs with the DAT is thought to be critically important for many of the actions of these drugs, including the reward and locomotor stimulating effects. The goal of the present paper was to compile recent data concerning the behavioral and pharmacological characteristics of DAT knock-out mice, especially the consequences of acute and chronic psychostimulant administration, such as the hypolocomotor response. The reinforcing potency of amphetamines, cocaine, and morphine maintained in the absence of the DAT may suggest that other neurotransmitter systems in addition to dopamine might contribute to the actions of psychostimulants and opioid agonists. In the absence of the DAT, these drugs could be acting on alternative targets, such as the serotonin or noradrenaline transporters. In summary, mice lacking the dopamine transporter gene may represent an excellent model to elucidate the molecular adaptive changes accompanying the pathological states associated with hyperdopaminergia, such as the attention deficit hyperactivity disorder in humans.
Biala
Grazyna
G
Katedra Farmakologii z Farmakodynamika Akademii Medycznej im. prof. F. Skubiszewskiego w Lublinie. gragab@panaceum.am.lublin.pl
D000222:Adaptation, Physiological; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006948:Hyperkinesis / Q000188:drug therapy* / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology
D000662:Amphetamines; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D009294:Narcotics; D009020:Morphine; D003042:Cocaine