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Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

Neuropsychopharmacology Laboratory, Mayo Foundation for Medical Education and Research Mayo Clinic Florida, 4500 San Pablo road, Jacksonville, FL 32224, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Behav. Sci. 2014, 4(1), 42-52;
Received: 14 November 2013 / Revised: 13 January 2014 / Accepted: 14 January 2014 / Published: 22 January 2014
(This article belongs to the Special Issue Management and Treatment of the Major Mental Disorders)
Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine. View Full-Text
Keywords: neurotensin; nicotine; cocaine; gateway drug; rat neurotensin; nicotine; cocaine; gateway drug; rat
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Fredrickson, P.; Boules, M.; Stennett, B.; Richelson, E. Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization. Behav. Sci. 2014, 4, 42-52.

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