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Behav Brain Res. 2014 Jun 1;266:108-18. doi: 10.1016/j.bbr.2014.02.044. Epub 2014 Mar 5.

The effects of N-acetylcysteine on cocaine reward and seeking behaviors in a rat model of depression.

Author information

1
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland. Electronic address: frankow@if-pan.krakow.pl.
2
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
3
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland; Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Kraków, Medyczna 9, Poland.

Abstract

Depression and substance-abuse (e.g., cocaine) disorders are common concurrent diagnoses. In the present study, we combined bilateral olfactory bulbectomy (OBX) with a variety of procedures of intravenous cocaine self-administration and extinction/reinstatement in rats. We also investigated the effects of N-acetylcysteine (NAC) on rewarding and seeking behaviors for cocaine in OBX rats and compared the drug's effects in sham-operated control animals (SHAM). The occurrence of depressive symptoms before introduction to cocaine self-administration enhanced subsequent cocaine-seeking behaviors but did not significantly influence cocaine's rewarding properties or extinction training. NAC (25-100mg/kg) given acutely or repeatedly did not alter the co-occurrence of cocaine reward and depression but effectively reduced the cocaine-seeking behavior observed in both phenotypes. Our results indicate that depression behavior is linked to more pronounced drug craving and a higher propensity to relapse in rats. We also show the lack of efficacy of repeated NAC treatment on SHAM or OBX animals in terms of cocaine self-administration, while the drug was an effective blocker of cocaine-seeking behavior in both studied phenotypes, with a more pronounced drug effect observed in OBX animals. The last finding demonstrates the potential clinical utility of NAC to reduce cocaine seeking enhanced by co-existing depression.

KEYWORDS:

Bulbectomy; Cocaine; Depression; N-acetylcysteine; Seeking-behavior; Self-administration

PMID:
24613240
DOI:
10.1016/j.bbr.2014.02.044
[Indexed for MEDLINE]

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