Chapter 18 P2 receptor-mediated activation of noradrenergic and dopaminergic neurons in the rat brain

Publisher Summary Focal electrical stimulation evokes in the rat locus coeruleus (LC) biphasic synaptic potentials consisting of early depolarizing (p.s.p.) and late hyperpolarizing (i.p.s.p.) components. It has been found that the p.s.p. is because of the release of glutamate from afferent fibres predominantly onto non-N-methyl-D- aspartate (non-NMDA) receptors and of γ-aminobutyric acid (GABA) onto GABAA receptors. In the chapter, the investigations demonstrate the presence of release stimulatory P2 receptors in the central noradrenergic and dopaminergic systems. Hence, exogenously applied or endogenously released ATP may excite noradrenergic neurons of the LC and dopaminergic neurons of the ventral tegmental area (VTA). ATP and its structural analog 2-MeSATP depolarized LC neurons in a slice preparation. In addition, there is strong evidence for the contribution of ATP to excitatory synaptic potentials recorded from the neurons themselves; this ATP appears to be coreleased with noradrenaline from recurrent axon collaterals or dendrites. A combined methodological approach was used to prove the presence of P2 receptors in the VTA and its main projection target in the NAc. Although electrophysiological recordings from VTA neurons in a slice preparation failed to show a depolarizing response to 2-MeSATP, the application of 2-MeSATP into the VTA via a microdialysis probe was a powerful stimulus of dopamine release in vivo.