title: Pharmacological manipulations of the pedunculopontine tegmental nucleus in the rat reduce self-administration of both nicotine and cocaine.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada. bill_corrigall@camh.net
authors.forename: William A
authors.initials: WA
authors.lastname: Corrigall
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Coen
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: LaurelK
authors.initials: L
authors.lastname: Adamson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D012601:Scopolamine / Q000494:pharmacology; D012646:Self Administration; D019966:Substance-Related Disorders / Q000188:drug therapy*; D013681:Tegmentum Mesencephali / Q000187:drug effects*
chemical_list: D002491:Central Nervous System Agents; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009538:Nicotine; D002217:Carbachol; D012601:Scopolamine; D003042:Cocaine