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Neurochemical Substrates of Menthol Actions in Reward‐Addiction Brain Areas.
Author(s) -
Davila-Garcia Martha Isabel,
Wang Paul,
Lin Stephen,
Dekhordi Ozra
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.07308
Subject(s) - ventral tegmental area , nucleus accumbens , menthol , conditioned place preference , dopaminergic , neuroscience , periaqueductal gray , nicotine , central nucleus of the amygdala , addiction , dopamine , chemistry , amygdala , psychology , midbrain , central nervous system , organic chemistry
Menthol, a commonly used flavoring additive in cigarettes has been found to facilitate smoke initiation and nicotine addiction. Menthol masks the harshness of nicotine, increases its absorption, and provides a cooling sensation that appeals to many smokers. In addition to its peripheral sensory impact, recent studies have demonstrated the presence of menthol in the CNS after in vivo exposure. This implies that menthol may also impact nicotine addiction through central mechanisms. In the present study in mice, we hypothesized that dopaminergic and GABAergic neurons of the reward‐addiction circuitry are among the initial targets of acute menthol in the CNS. We tested this hypothesis by utilizing c‐Fos immunohistochemical technique together with double labeling to identify anatomical location of menthol activated cells with respect to tyrosine hydroxylase (TH) immunoreactive (TH‐IR) dopaminergic and GAD67‐GFP positive GABAergic cells. Menthol (80 mM, IP), produced c‐Fos activation at multiple sites of the mesocorticolimbic reward‐addiction pathways including several structures previously shown to be activated by nicotine such as the periaqueductal gray (PAG), dorsal raphe (DR), ventral tegmental area (VTA), amygdala, nucleus accumbens (NAcc), anterior olfactory nucleus (AON) and cingulate‐orbitofrontal cortex (A25/MO). However, none of the dopaminergic neurons in VTA, PAG/DR region or hypothalamus were activated by IP administration of menthol. Moreover, GABAergic cells of VTA, NAcc, or A25/MO were not the initial targets of menthol at these sites. In summary, the present study identifies several sites, including those of the mesocorticolimbic reward‐addiction pathways that are activated by acute IP administration of menthol, however, none contained dopaminergic and GABAergic neurons. Support or Funding Information This work was supported by grants from Charles and Mary Latham Funds and Howard University Bridge Funds and Pilot Study Awards Program (BFPSAP). The authors acknowledge use of the resources provided by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number G12MD007597.