Amphetamine-induced release of dendritic dopamine in substantia nigra pars reticulata: D1-mediated behavioral and electrophysiological effects

Abstract

Dopamine (DA) released from dendrites of substantia nigra dopaminergic neurons potentially is in a position to modulate basal ganglia outputs from the substantia nigra pars reticulata (SNR) via stimulation of D1 receptors on the terminals of striatonigral afferents. The effects of endogenous DA release in the SNR were examined in rats using behavioral activation, multiunit activity of SNR neurons, and cortical EEG pattern as dependent measures. Unilateral infusion of amphetamine (AMPH) into SNR (10 micrograms/0.5 microliter; 5 min) produced a short-lasting behavioral activation that was blocked by coinfusion of the D1 DA receptor antagonist SCH 23390 (0.5 micrograms). Multiunit recordings of SNR neurons in anesthetized rats showed that AMPH, infused as above, produced a rapid decrease in SNR activity. This decrease was maximal (approximately 90%) during the first 10 min postinfusion, followed by a gradual return to baseline levels. Coinfusion of SCH 23390 blocked the AMPH-induced decrease in SNR activity, although by itself this drug produced a 40% decrease in activity. Cortical EEG acquired during the SNR infusions/recordings showed a short-duration change in pattern immediately after AMPH infusion. A relative shift in power from the lowest frequency interval determined (0.8-2.7 Hz) to the next higher frequency interval (2.7-6.8 Hz) was observed which could be prevented by coinfusion of SCH 23390. Thus, dendritically released DA can inhibit the activity of SNR neurons via local stimulation of D1 receptors. This effect is associated with a brief behavioral activation and EEG desynchronization.

Substantia Nigra D1Receptors and Stimulation of Striatal Cholinergic Interneurons by Dopamine: A Proposed Circuit Mechanism

“…Nigral D 1 receptors are localized exclusively on the terminals of the GABAergic striatonigral projection (Porceddu et al, 1986;Yung et al, 1995), and stimulation of these receptors seems to modulate positively the release of GABA from these sites (Floran et al, 1990;C ameron and Williams, 1993). In turn, an enhanced inhibitory drive to the GABAergic nigrothalamic projection neurons could disinhibit thalamocortical activity (Deniau and Chevalier, 1985;Timmerman and Abercrombie, 1996) and increase the level of glutamate input to striatal cholinergic neurons. In support of this model, previous work indicates that somatodendritic dopamine release can elevate a variety of indices of thalamocortical activation (Wilson and Wightman, 1985;Gauchy et al, 1987;Robertson and Robertson, 1987;LaHoste and Marshall, 1990;Yurek and Hipkins, 1993;Timmerman and Abercrombie, 1996).…”

“…In turn, an enhanced inhibitory drive to the GABAergic nigrothalamic projection neurons could disinhibit thalamocortical activity (Deniau and Chevalier, 1985;Timmerman and Abercrombie, 1996) and increase the level of glutamate input to striatal cholinergic neurons. In support of this model, previous work indicates that somatodendritic dopamine release can elevate a variety of indices of thalamocortical activation (Wilson and Wightman, 1985;Gauchy et al, 1987;Robertson and Robertson, 1987;LaHoste and Marshall, 1990;Yurek and Hipkins, 1993;Timmerman and Abercrombie, 1996). Moreover, reverse dialysis in the striatum of the noncompetitive NMDA receptor antagonist (5R,10S )-(ϩ)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (M K 801) has been reported to attenuate the increase in striatal ACh release produced by systemic administration of the dopamine D 1 receptor agonist C Y 208-243 .…”

High-Dose Methamphetamine Acutely Activates the Striatonigral Pathway to Increase Striatal Glutamate and Mediate Long-Term Dopamine Toxicity

“…and Abercrombie, 1996;Matuszewich and Yamamoto, 1999). It is uncertain if SNr GABA measured in our study originates from striatonigral or pallidonigral terminals.…”

Dopamine spillover after quantal release: Rethinking dopamine transmission in the nigrostriatal pathway

“…Somatodendritic release of DA in the SNc, as well as axonal DA release in the striatum are necessary for basal ganglia-mediated motor behaviors (Robertson and Robertson, 1989;Timmerman and Abercrombie, 1996;Bergquist et al, 2003). Transporters for DA (DATs) are expressed exclusively by DA neurons and are found extrasynaptically on DA axons in striatum and on DA somata and dendrites in midbrain Nirenberg et al, 1996;Hersch et al, 1997).…”