[Purinergic modulation of the brain dopaminergic transmission: behavioral-pharmacologic conclusions].
The ventral tegmental area (VTA), the prefrontal cortex and the nucleus accumbens (NAc) are key elements of the mesolimbic dopaminergic system. Dopaminergic neurotransmission in the NAc is essential in the regulation of motor activity and reward. Extracellular ATP by activating P2 receptors may function as a neurotransmitter or a neuromodulator. We showed that P2 receptors are expressed both in the NAc and VTA, and their activation (probably of the P2Y1 subtype) results in increased dopamine release. It leads to complex neurophysiologic and behavioral changes. We observed activation of the EEG: an elevation of the absolute EEG power and the power in the alpha-frequency band as well as decrease in the delta-frequency band. Behavioral studies demonstrated that activation of P2 receptors elicited more consistent and stronger goal-directed locomotor activity in response to the stimulus of a novel environment. P2Y receptors were also involved in regulation of feeding, their inhibition decreased the amount and the duration of feeding. On the other hand, in various behavioral functions, P2 receptor-mediated glutamate release or the activation of the adenosine receptors counterbalanced the actions mediated by ATP-induced dopamine release. We also showed that enhancement of the P2Y1 receptor expression may be involved in adaptive changes of the mesolimbic system such as behavioral sensitization to repeated amphetamine administration. In summary, the mesolimbic dopaminergic system is modulated via P2Y purinergic receptors, and it may lead to complex behavioral pharmacological changes.
Köles
László
L
Lipcsei Egyetem, Rudolph Boehm Farmakológiai es Toxikológiai Intézet, Németország.
Gerevich
Zoltán
Z
Kittner
Holger
H
Krügel
Ute
U
Franke
Heike
H
Illés
Péter
P
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004569:Electroencephalography; D005247:Feeding Behavior / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008032:Limbic System / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; C546382:P2RY1 protein, human; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D018698:Glutamic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000661:Amphetamine; D004298:Dopamine