Pharmacological manipulations of the pedunculopontine tegmental nucleus in the rat reduce self-administration of both nicotine and cocaine
Abstract
Rationale The pedunculopontine tegmental nucleus (PPTg) has been implicated in the self-administration of drugs, particularly nicotine, which acts directly through the PPTg in addition to targeting midbrain dopamine neurons. The direct action of nicotine in PPTg may be through GABAergic mechanisms that have been shown to influence nicotine self-administration preferentially compared to cocaine.Objective The purpose of these experiments was to examine several pharmacological manipulations that alter neuronal activity in the PPTg for their specificity or generality in nicotine versus cocaine reinforcement.Methods and results Rats trained to self-administer nicotine or cocaine intravenously were prepared with brain microcannulae directed to the PPTg. Intra-PPTg microinfusions of the muscarinic agonist carbachol (0.1-1.0 microg), the micro opioid agonist DAMGO (0.005 and 0.05 microg), tetrodotoxin (5 ng) and neostigmine (0.5 nmol) each reduced the self-administration of nicotine and cocaine maintained on an FR5 schedule of reinforcement. The muscarinic antagonist scopolamine (0.1-1.0 microg) and the opioid antagonist CTOP (1 microg) did not affect self-administration, but reversed the effects of the respective agonist when co-administered with it. Carbachol and DAMGO were also tested in self-administration maintained on a progressive-ratio schedule; each agonist again reduced both nicotine and cocaine self-administration.Conclusions PPTg manipulations are able to alter established self-administration of nicotine, which acts at the level of the ventral tegmental area and the PPTg itself, and cocaine, which acts through the mesolimbic dopamine system. These data suggest that the PPTg is an important substrate in drug dependence.
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Stimulation of nicotinic receptors and M5-type muscarinic receptors increases the tonic excitability of dopamine neurons.
“Stimulation of nAChR and M5-type mAChRs increases the tonic excitability of these DA neurons (Corrigall et al., 2002; Miller and Blaha, 2005; Yeomans and Baptista, 1997).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Corrigall et al., 2002
Disruption of PPTg activity decreases the rewarding and locomotor effects of drugs of abuse such as cocaine and nicotine.
“At the behavioral level, this conclusion is consistent with the finding that disruption of PPTg activity decreases the rewarding and locomotor effects of drugs of abuse such as cocaine and nicotine (Champtiaux et al., 2006; Corrigall et al., 1994; Corrigall et al., 2002), while lesion of NAc cholinergic neurons increases cocaine self-administration, as might be expected if a pause in cholinergic”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Corrigall et al., 2002
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Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
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Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors
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- Authors
- Corrigall, W., Coen, K., Zhang, J., & Adamson, L.
- Affiliations
- University of Toronto (CA)
- Centre for Addiction and Mental Health (CA)
- Venue
- Psychopharmacology
- Published
- 2002-03-01
- Volume
- 160
- Issue
- 2
- Pages
- 198-205
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2064322520
- Cited by
- 79
- References
- 9
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da009577-06)
- National Institute on Drug Abuse (DA 09577)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- pedunculopontine nucleus, nicotine self-administration, cocaine self-administration, drug reinforcement, carbachol, muscarinic agonists, DAMGO, opioid agonists, tetrodotoxin, neostigmine, scopolamine, CTOP, GABAergic mechanisms, mesolimbic dopamine system, ventral tegmental area, drug addiction, progressive ratio schedule
- MeSH terms
- Animals, Behavior, Animal, Carbachol, Central Nervous System Agents, Cocaine, Male, Nicotine, Scopolamine, Self Administration, Tegmentum Mesencephali, Substance-Related Disorders, Rats, Long-Evans, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Rats
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