Glutamate and GABA modulate dopamine in the pedunculopontine tegmental nucleus

Abstract

The pedunculopontine tegmental nucleus (PPTg) has an important anatomical position connecting basal ganglia and limbic systems with motor execution structures in the pons and spinal cord. It receives glutamatergic and GABAergic input and has additional reciprocal connections with mesencephalic dopaminergic neurons, suggesting that the PPTg plays a key role in frontostriatal information processing. In vivo microdialysis in freely moving rats, in combination with behavioral analysis, was used in this study to investigate whether the dopaminergic input can be modulated at the level of the PPTg via N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) or GABA(B) receptors. Stimulation of the GABA(B) receptor decreased dopamine release in the PPTg while that of the AMPA and NMDA receptors increased it. A time-related comparison of the effects of NMDA (0.75 and 1 mM) and AMPA (50 and 25 microM) revealed a more long-lasting effect after AMPA stimulation than after NMDA. However, only the infusion of the GABA(B) receptor agonist baclofen (100 and 200 microM) stimulated stereotyped behavior (e.g. sniffing, digging or head movements) and contralateral circling. This study clearly demonstrates that GABAergic as well as glutamatergic terminals in the PPTg are critically involved in the modulation of the dopamine system. Moreover, a decrease in PPTg dopamine via GABA(B) receptor stimulation seems to be behaviorally relevant.

Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates

“…For example, Hotsenpiller and Wolf (2003) recently demonstrated that baclofen attenuates conditioned locomotion to cues associated with cocaine administration, and also modulates extracellular glutamate levels in the NAc. Moreover, Steninger and Kretschmer (2003) report that baclofen infused into the pedunculopontine tegmental Fig. 5 Changes in DA efflux in the NAc (line graph) and dAMPH self-administration (bar graph) following baclofen pretreatment in sessions of representative animals.…”

Change in Brainstem Gray Matter Concentration Following a Mindfulness-Based Intervention is Correlated with Improvement in Psychological Well-Being

“…The pedunculopontine nucleus and laterodorsal tegmental nucleus neurons send axons to dopamine-containing areas of the ventral tegmental area and the substantia nigra, as well as to the lateral hypothalamus, thalamus, and basal ganglia, wherein glutamine and acetylcholine may act to modulate reward and learning (Yeomans et al, 1993; Steiniger and Kretschmer, 2003). In addition, the pedunculopontine nucleus may play a role in associative learning and reward as a relay for contextual information to midbrain dopamine neurons (Pan and Hyland, 2005).…”

Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

“…In rat, dopamine was detected using radiometric assays or microdialysis in the CnF (Versteeg et al, 1976; Saavedra et al, 1979) and PPN (Steiniger and Kretschmer, 2003) that are both part of the MLR in mammals (see Ryczko and Dubuc, 2013). Moreover, dopaminergic fibers were detected in rat brainstem using immunohistochemistry (Kitahama et al, 2000).…”