Responses of limbic and extrapyramidal substance P systems to nicotine treatment.
BACKGROUND
Neuropeptides are linked to the psychopathology of stimulants of abuse, principally through dopamine mechanisms. Substance P (SP) is one of these neuropeptides and is associated with both limbic and extrapyramidal dopaminergic pathways and likely contributes to the pharmacology of these stimulants. The effects of nicotine on these dopamine systems have also been extensively studied; however, its effects on the associated SP pathways have received little attention.


OBJECTIVE
In the present study, we elucidated the effects of nicotine treatment on limbic and extrapyramidal SP systems by measuring changes in associated SP tissue concentrations.


METHODS
Male Sprague-Dawley rats received (+/-)nicotine 4.0 mg/kg/day (0.8 mg/kg, intraperitoneally; five injections at 2-h intervals) in the presence or absence of selective dopamine D1 and D2 receptor antagonists or a nonselective nicotinic acetylcholine receptor antagonist.


RESULTS
The nicotine treatment significantly but temporarily decreased substance P-like immunoreactivity (SPLI) content in the ventral tegmental area (VTA) and substantia nigra 12-18 h after drug exposure. The nicotine-mediated changes in SPLI were selectively blocked by pretreatment with mecamylamine as well as a dopamine D1, D2, or both receptor antagonists. Other brain areas that also selectively demonstrated nicotine-related declines in SPLI content included prefrontal cortex, the nucleus accumbens shell, and the very posterior caudate.


CONCLUSIONS
These findings indicate that some limbic and basal ganglia SP systems are significantly affected by exposure to nicotine through processes mediated by nicotinic and dopaminergic receptors, suggesting a role for SP pathways in nicotine's limbic and extrapyramidal effects.
Alburges
Mario E
ME
Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT, USA. mario.alburges@utah.edu
Frankel
Paul S
PS
Hoonakker
Amanda J
AJ
Hanson
Glen R
GR
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D005116:Extrapyramidal Tracts / Q000187:drug effects / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000187:drug effects* / Q000378:metabolism
D018722:Nicotinic Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013373:Substance P; D009538:Nicotine
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