TY - JOUR
T1 - Menthol enhances nicotine-induced locomotor sensitization and in vivo functional connectivity in adolescence
AU - Thompson, Matthew F.
AU - Poirier, Guillaume L.
AU - Dávila-García, Martha I.
AU - Huang, Wei
AU - Tam, Kelly
AU - Robidoux, Maxwell
AU - Dubuke, Michelle L.
AU - Shaffer, Scott A.
AU - Colon-Perez, Luis
AU - Febo, Marcelo
AU - DiFranza, Joseph R.
AU - King, Jean A.
N1 - Funding Information:
After an initial acclimation period, the animals were handled with their cage mate and given subcutaneous (s.c.) saline (1 mg/ kg, s.c.) once daily for two days prior to the start of locomotor testing. All open-field experiments were performed during the dark phase of the light-dark cycle. All procedures were in accordance with National Institutes of Health (NIH) guidelines and approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Massachusetts Medical School.
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this project was provided by NIH grants R01 DA 021846, R01 DA 025690, and S10 OD018132-01 to JA King.
Publisher Copyright:
© 2017, © The Author(s) 2017.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Mentholated cigarettes capture a quarter of the US market, and are disproportionately smoked by adolescents. Menthol allosterically modulates nicotinic acetylcholine receptor function, but its effects on the brain and nicotine addiction are unclear. To determine if menthol is psychoactive, we assessed locomotor sensitization and brain functional connectivity. Adolescent male Sprague Dawley rats were administered nicotine (0.4 mg/kg) daily with or without menthol (0.05 mg/kg or 5.38 mg/kg) for nine days. Following each injection, distance traveled in an open field was recorded. One day after the sensitization experiment, functional connectivity was assessed in awake animals before and after drug administration using magnetic resonance imaging. Menthol (5.38 mg/kg) augmented nicotine-induced locomotor sensitization. Functional connectivity was compared in animals that had received nicotine with or without the 5.38 mg/kg dosage of menthol. Twenty-four hours into withdrawal after the last drug administration, increased functional connectivity was observed for ventral tegmental area and retrosplenial cortex with nicotine+menthol compared to nicotine-only exposure. Upon drug re-administration, the nicotine-only, but not the menthol groups, exhibited altered functional connectivity of the dorsal striatum with the amygdala. Menthol, when administered with nicotine, showed evidence of psychoactive properties by affecting brain activity and behavior compared to nicotine administration alone.
AB - Mentholated cigarettes capture a quarter of the US market, and are disproportionately smoked by adolescents. Menthol allosterically modulates nicotinic acetylcholine receptor function, but its effects on the brain and nicotine addiction are unclear. To determine if menthol is psychoactive, we assessed locomotor sensitization and brain functional connectivity. Adolescent male Sprague Dawley rats were administered nicotine (0.4 mg/kg) daily with or without menthol (0.05 mg/kg or 5.38 mg/kg) for nine days. Following each injection, distance traveled in an open field was recorded. One day after the sensitization experiment, functional connectivity was assessed in awake animals before and after drug administration using magnetic resonance imaging. Menthol (5.38 mg/kg) augmented nicotine-induced locomotor sensitization. Functional connectivity was compared in animals that had received nicotine with or without the 5.38 mg/kg dosage of menthol. Twenty-four hours into withdrawal after the last drug administration, increased functional connectivity was observed for ventral tegmental area and retrosplenial cortex with nicotine+menthol compared to nicotine-only exposure. Upon drug re-administration, the nicotine-only, but not the menthol groups, exhibited altered functional connectivity of the dorsal striatum with the amygdala. Menthol, when administered with nicotine, showed evidence of psychoactive properties by affecting brain activity and behavior compared to nicotine administration alone.
KW - adolescence
KW - menthol
KW - nicotine
KW - Smoking
KW - tobacco
UR - http://www.scopus.com/inward/record.url?scp=85042524415&partnerID=8YFLogxK
U2 - 10.1177/0269881117719265
DO - 10.1177/0269881117719265
M3 - Article
C2 - 28747086
AN - SCOPUS:85042524415
SN - 0269-8811
VL - 32
SP - 332
EP - 343
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
IS - 3
ER -