[Abstract Title]. - Society for Neuroscience

Abstract: It is widely accepted that several effects of nicotine are mediated by increased
dopamine (DA) release in the terminal fields of the mesencephalic dopaminergic systems.
However, there is also evidence that nicotine may influence several other neurotransmitters that
can indirectly affect the DA systems. In particular presynaptic interaction between glutamatergic
and cholinergic systems has been reported to play an important role in the mechanism of action
of nicotine, possibly via modulation of DA.
The objective of this study was to investigate the effects of chronic administration of (-)nicotine
on the function of the N-methyl-D-aspartate (NMDA) presynaptic receptors modulating [3H]DA
release in rat prefrontal cortex (PFC) and nucleus accumbens (NAc) using rat superfused nerve
endings. In the PFC synaptosomes, prelabelled with [3H]DA, NMDA in a concentrationdependent
manner evoked [3H]DA release in rats chronically treated with vehicle (14 days; via
osmotic mini-pumps) with an apparent affinity of 13.1 ± 2 κM. The NMDA evoked overflow of
the [3H]DA in PFC nerve endings of rats treated with (-)nicotine (14 days; 0.125 mg/Kg/h) was
significantly lower (-43%) than in vehicle treated rats. The apparent affinity was 9 ± 1.4 κM.
Exposure of NAc synaptosomes of rats treated with vehicle to different concentration of NMDA
produced an increase of [3H]DA overflow with an EC50 of. 14.5 ± 5.5 κM. This effect was
significantly potentiated in synaptosomes from animals chronically treated with (-)nicotine
suggesting an up-regulation of the NMDA presynaptic heteroreceptor. The EC50 was 10.5 ± 0.5
κM. The K+-evoked exocytotic release of [3H]DA was not modified by the long term (-)nicotine
administration. Both the up-and downregulation of the NMDA receptors disappeared after 14
days withdrawal. The results show
that chronic (-)nicotine differentially affects the function of presynaptic NMDA receptors which
regulate [3H]DA release in the PFC and NAc of the rat.
This work was supported by research contract with GlaxoSmithKline SpA and by Italian MIUR.
Disclosures: M. Marchi , GlaxoSmithKline SpA, B. Research Grant (principal investigator,
collaborator or consultant and pending grants as well as grants already received); E. Merlo-Pich,
None; M. Grilli, None; A. Pittaluga, None.
Poster
258. Molecular and Neurochemical Basis of Nicotine Addiction
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 258.14/AA17
Topic: B.02.c. Nicotinic acetylcholine receptors: regulation and function
Support: NS42091
TRDRP 15FT-0073