Citation

Vieira-Brock PL, McFadden LM, Nielsen SM, Smith MD, Hanson GR, Fleckenstein AE. Int. J. Neuropsychopharmacol. 2015; ePub(ePub): ePub.

Affiliation

School of Dentistry, University of Utah, Salt Lake City, UT 84112 annette.fleckenstein@hsc.utah.edu.

Copyright

(Copyright © 2015, Cambridge University Press)

DOI

10.1093/ijnp/pyv073

PMID

26164716

Abstract

BACKGROUND: Previous studies have demonstrated that methamphetamine (METH) abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine (NIC) prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors (nAChRs). The present study investigated whether NIC attenuates METH-induced novel object recognition (NOR) deficits in rats and explored potential underlying mechanisms.

METHODS: Adolescent or adult male Sprague-Dawley rats received either NIC water (10-75 μg/ml) or tap water for several weeks. METH (4 x 7.5 mg/kg/injection) or saline was administered either before or after chronic NIC exposure. Novel object recognition was evaluated 6 d after METH or saline. Serotonin transporter function and density, and α4β2 nAChR density were assessed on the following day.

RESULTS: Chronic NIC intake via drinking water beginning during either adolescence or adulthood attenuated the NOR deficits caused by a high-dose METH administration. Similarly, NIC attenuated METH-induced deficits in NOR when administered after METH treatment. However, NIC did not attenuate the serotonergic deficits caused by METH in adults. Conversely, NIC attenuated METH-induced deficits in α4β2 nAChR density in the hippocampal CA1 region. Furthermore, NIC increased α4β2 nAChR density in the hippocampal CA3, dentate gyrus and perirhinal cortex (PRh) in both saline- and METH-treated rats.

CONCLUSIONS: Overall, these findings suggest that NIC-induced increases in α4β2 nAChRs in the hippocampus and PRh might be one mechanism by which NOR deficits are attenuated by NIC in METH-treated rats.

Language: en