Effects of nornicotine enantiomers on intravenous S(-)-nicotine self-administration and cardiovascular function in rats.
Psychopharmacology (Berl)
; 190(2): 145-55, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17096082
ABSTRACT
RATIONALE Previous neurochemical evidence indicates that R(+)-nornicotine is more potent than S(-)-nornicotine in evoking dopamine release in rat nucleus accumbens slices. OBJECTIVE:
The current study tested the hypothesis that R(+)-nornicotine is also more potent than S(-)-nornicotine in selectively decreasing intravenous S(-)-nicotine self-administration in rats.RESULTS:
After acute pretreatment (1-10 mg/kg for each enantiomer), R(+)-nornicotine was more potent than S(-)-nornicotine in decreasing S(-)-nicotine self-administration; in contrast, within the same dose range, the nornicotine enantiomers were equipotent in decreasing sucrose-maintained responding. This enantioselectivity does not likely reflect a difference in bioavailability, since similar levels of nornicotine were recovered from the brain 60 min after injection (5.6 mg/kg for each enantiomer). With repeated pretreatment, tolerance did not develop to the rate-decreasing effect of either nornicotine enantiomer (3 or 5.6 mg/kg) with respect to the decrease in S(-)-nicotine self-administration, although the enantioselectivity dissipated across repeated pretreatments. While both enantiomers acutely produced a similar increase in blood pressure and heart rate, tolerance developed to the blood pressure effects of R(+)-nornicotine, but not to the effects of S(-)-nornicotine, across repeated treatments.CONCLUSION:
Both R(+)- and S(-)-nornicotine may have potential utility as a novel tobacco use cessation agent.
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Banco de datos:
MEDLINE
Asunto principal:
Tabaquismo
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Presión Sanguínea
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Frecuencia Cardíaca
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Motivación
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Nicotina
Límite:
Animals
Idioma:
En
Año:
2007
Tipo del documento:
Article