GABA mechanisms in the pedunculopontine tegmental nucleus influence particular aspects of nicotine self-administration selectively in the rat.
BACKGROUND
The pedunculopontine tegmental nucleus (PPTg) is part of the neuronal circuit activated by self-administered nicotine. The cholinergic neurons of the PPTg comprise a prominent projection to midbrain dopamine neurons. However, anatomical studies of Fos expression suggest that nicotine targets primarily non-cholinergic neurons in the PPTg, especially GABAergic and glutamatergic neurons.


OBJECTIVE
The objective of these experiments was to examine the role of GABA manipulations in the PPTg on nicotine self-administration.


RESULTS
Rats trained to self-administer nicotine or cocaine intravenously were prepared with brain microcannulae directed to the PPTg. Intra-PPTg microinfusions of the GABA agonists muscimol (10-50 ng) and baclofen (30-60 ng) reduced nicotine self-administration maintained on a fixed-ratio schedule of reinforcement (30 microg/kg per infusion); self-administration of cocaine (0.3 mg/kg per infusion) under an identical schedule was not affected. Muscimol and baclofen were also examined after intra-PPTg microinfusion in animals trained to self-administer nicotine on a progressive-ratio schedule (10 and 30 microg/kg per infusion). Progressive-ratio responding was sensitive to pharmacological manipulations such as a change in the nicotine dose available for self-administration, or intra-PPTg microinfusion of the nicotinic antagonist dihydro-beta-erythroidine (30 microg). However, nicotine self-administration on a progressive-ratio schedule was not altered by intra-PPTg microinfusions of GABA agonists.


CONCLUSIONS
These data confirm that the PPTg is involved in nicotine self-administration, a conclusion that is independent of the schedule of reinforcement that is used. GABAergic mechanisms in the PPTg play a selective role in nicotine reinforcement compared to cocaine, and that role is restricted to the characteristics of reinforcement measured by fixed-ratio responding.
Corrigall
W A
WA
Smoking and Nicotine Dependence Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada M5S 2S1. bill_corrigall@camh.net
Coen
K M
KM
Zhang
J
J
Adamson
K L
KL
D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012646:Self Administration; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D018755:GABA Agonists; D018722:Nicotinic Agonists; D009538:Nicotine; D003042:Cocaine