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Acetylcholine from the mesopontine tegmental nuclei differentially affects methamphetamine induced locomotor activity

Lauren K Dobbs1, Gregory P Mark

  • 1Department of Behavioral Neuroscience, Oregon Health & Sciences University, School of Medicine, 3181 Sam Jackson Park Rd., Portland, OR 97239, United States. dobbsl@ohsu.edu

Behavioural Brain Research
|September 28, 2011
PubMed

Insights

Laterodorsal tegmental (LDT) acetylcholine (ACh) influences methamphetamine (MA) effects on locomotion and brain chemistry. LDT-derived ACh is crucial for MA-induced locomotor activity and the cholinergic, but not dopaminergic, response to MA.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Methamphetamine (MA) elevates dopamine (DA) in the mesolimbic pathway and acetylcholine (ACh) in the ventral tegmental area (VTA).
  • The laterodorsal tegmental (LDT) and pedunculopontine tegmental (PPT) nuclei are primary sources of VTA cholinergic input.
  • The specific roles of LDT- and PPT-derived ACh in MA's effects on DA, ACh, and locomotion are not fully understood.

Purpose of the Study:

  • To investigate the contribution of LDT-derived ACh to MA-induced locomotor activation.
  • To determine the individual roles of LDT and PPT ACh in modulating MA-induced ACh and DA levels in the VTA and nucleus accumbens (NAc).

Main Methods:

  • Reversible inhibition of LDT neurons using intra-LDT microinjections of the M2 receptor agonist oxotremorine (OXO) in mice.
  • Assessment of locomotor activity following OXO administration before saline or MA injection.
  • In vivo microdialysis in the VTA and NAc to measure ACh and DA levels after intra-LDT or intra-PPT OXO administration.

Main Results:

  • High-dose OXO in the LDT significantly reduced both saline- and MA-induced locomotor activity.
  • Intra-LDT OXO dose-dependently attenuated the MA-induced increase in VTA ACh levels.
  • Neither intra-LDT nor intra-PPT OXO affected MA-induced DA levels in the NAc, and intra-PPT OXO did not alter ACh levels in the VTA.

Conclusions:

  • ACh originating from the LDT, but not the PPT, plays a significant role in locomotor behavior.
  • LDT-derived ACh is critical for the cholinergic, but not the dopaminergic, neurochemical response to systemic MA.
  • These findings highlight the specific involvement of LDT cholinergic pathways in mediating behavioral and neurochemical effects of MA.

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