Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.
Cholinergic input to the ventral tegmental area (VTA) is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg) provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII), the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65)% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland, United States of America.
Stephan
S
Steidl
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland, United States of America.
Huiling
H
Wang
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland, United States of America.
Roy A
RA
Wise
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D018678:Cholinergic Agents / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003042:Cocaine / Q000008:administration & dosage*; D003213:Conditioning, Psychological; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D003932:Heroin / Q000008:administration & dosage*; D008297:Male; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D020318:Rats, Long-Evans; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000633:toxicity; D012646:Self Administration; D019966:Substance-Related Disorders / Q000378:metabolism / Q000473:pathology*; D014579:Urotensins / Q000008:administration & dosage
D018678:Cholinergic Agents; D004167:Diphtheria Toxin; D009498:Neurotoxins; D011993:Recombinant Fusion Proteins; D014579:Urotensins; D003932:Heroin; C029677:urotensin II; D003042:Cocaine; D000109:Acetylcholine; D004298:Dopamine