TY - JOUR
T1 - Minocycline reduced craving for cigarettes but did not affect smoking or intravenous nicotine responses in humans
AU - Sofuoglu, Mehmet
AU - Waters, Andrew J.
AU - Mooney, Marc
AU - O'Malley, Stephanie S.
PY - 2009/3
Y1 - 2009/3
N2 - In recent preclinical studies, the role of nitric oxide (NO) in nicotine dependence has become increasingly evident. Inhibition of NO synthesis blocks acquisition of conditioned place preference, and attenuates the nicotine abstinence syndrome in rodents. These findings have not been followed up in human studies. In order to obtain preliminary data on NO inhibition in human smokers, we conducted a randomized, double-blind, crossover study (N = 12) of minocycline, a tetracycline derivative antibiotic, that inhibits the neuronal nitric oxide (NO) synthase enzyme with resultant inhibition of NO production. Medication effects were assessed through a smoking choice procedure as well as subjective and physiological responses to nicotine administered via the intravenous route (IV). Minocycline treatment did not affect smoking self-administration in our choice procedure and did not affect most of the subjective responses to IV nicotine or sample smoking. Following IV nicotine administration, there was a greater reduction in craving for cigarettes under minocycline, compared to placebo. Similarly, smokers had greater reduction in their craving for cigarettes following sample smoking under minocycline treatment. These findings provide limited support for the potential use of minocycline as a treatment of nicotine dependence.
AB - In recent preclinical studies, the role of nitric oxide (NO) in nicotine dependence has become increasingly evident. Inhibition of NO synthesis blocks acquisition of conditioned place preference, and attenuates the nicotine abstinence syndrome in rodents. These findings have not been followed up in human studies. In order to obtain preliminary data on NO inhibition in human smokers, we conducted a randomized, double-blind, crossover study (N = 12) of minocycline, a tetracycline derivative antibiotic, that inhibits the neuronal nitric oxide (NO) synthase enzyme with resultant inhibition of NO production. Medication effects were assessed through a smoking choice procedure as well as subjective and physiological responses to nicotine administered via the intravenous route (IV). Minocycline treatment did not affect smoking self-administration in our choice procedure and did not affect most of the subjective responses to IV nicotine or sample smoking. Following IV nicotine administration, there was a greater reduction in craving for cigarettes under minocycline, compared to placebo. Similarly, smokers had greater reduction in their craving for cigarettes following sample smoking under minocycline treatment. These findings provide limited support for the potential use of minocycline as a treatment of nicotine dependence.
KW - Intravenous nicotine
KW - Minocycline
KW - Nicotine dependence
KW - Nitric oxide
KW - Nitric oxide synthase
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U2 - 10.1016/j.pbb.2008.11.004
DO - 10.1016/j.pbb.2008.11.004
M3 - Article
C2 - 19041336
AN - SCOPUS:58549104107
SN - 0091-3057
VL - 92
SP - 135
EP - 140
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 1
ER -