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. 2024 Jan 9;14(1):63.
doi: 10.3390/brainsci14010063.

Chronic Nicotine Consumption and Withdrawal Regulate Melanocortin Receptor, CRF, and CRF Receptor mRNA Levels in the Rat Brain

Oguz Gozen  1   2 , Buket Aypar  1 , Meliha Ozturk Bintepe  1 , Fulya Tuzcu  1 , Burcu Balkan  1   2 , Ersin O Koylu  1   2 , Lutfiye Kanit  1   2 , Aysegul Keser  1   2
Affiliations

Chronic Nicotine Consumption and Withdrawal Regulate Melanocortin Receptor, CRF, and CRF Receptor mRNA Levels in the Rat Brain

Oguz Gozen et al. Brain Sci. .

Abstract

Alterations in the various neuropeptide systems in the mesocorticolimbic circuitry have been implicated in negative effects associated with drug withdrawal. The corticotropin-releasing factor (CRF) and α-melanocyte-stimulating hormone are two peptides that may be involved. This study investigated the regulatory effects of chronic nicotine exposure and withdrawal on the mRNA levels of melanocortin receptors (MC3R, MC4R), CRF, and CRF receptors (CRFR1 and CRFR2) expressed in the mesocorticolimbic system. Rats were given drinking water with nicotine or without nicotine (control group) for 12 weeks, after which they continued receiving nicotine (chronic exposure) or were withdrawn from nicotine for 24 or 48 h. The animals were decapitated following behavioral testing for withdrawal signs. Quantitative real-time PCR analysis demonstrated that nicotine exposure (with or without withdrawal) increased levels of CRF and CRFR1 mRNA in the amygdala, CRF mRNA in the medial prefrontal cortex, and CRFR1 mRNA in the septum. Nicotine withdrawal also enhanced MC3R and MC4R mRNA levels in different brain regions, while chronic nicotine exposure was associated with increased MC4R mRNA levels in the nucleus accumbens. These results suggest that chronic nicotine exposure and withdrawal regulate CRF and melanocortin signaling in the mesocorticolimbic system, possibly contributing to negative affective state and nicotine addiction.

Keywords: CRF; CRF1 receptor; MC3R; MC4R; mesocorticolimbic system; nicotine; withdrawal.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Timeline of the experimental design.
Figure 2
Figure 2
Effect of nicotine consumption in water for 12 weeks and withdrawal on the body weight of rats measured before sacrifice. Body weight was lower after chronic nicotine exposure (no withdrawal, 0-W), 24 h withdrawal (24-W), and 48 h withdrawal (48-W) compared to controls. Bars represent the mean ± standard error of mean; * p < 0.05 (n = 10 per group).
Figure 3
Figure 3
Comparison of MC3R mRNA levels in septum (SEP), medial hypothalamic area (MHA) and the ventral tegmental area (VTA), and in rats following chronic nicotine exposure (0-W), 24 h withdrawal (24-W), and 48 h withdrawal (48-W). Bars represent the mean ± standard error of mean; * p < 0.05, ** p ≤ 0.01 (n = 8–10 per group).
Figure 4
Figure 4
MC4R mRNA levels in the medial hypothalamic area (MHA), amygdala (AMG), hippocampus (HIP), septum (SEP), dorsal striatum (DST), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in rats following chronic nicotine exposure (0-W), 24 h withdrawal (24-W), or 48 h withdrawal (48-W). Bars represent the mean ± standard error of mean; * p < 0.05, ** p < 0.01 (n = 8–10 per group).
Figure 5
Figure 5
Comparison of CRF mRNA levels in the ventral tegmental area (VTA), medial hypothalamic area (MHA), amygdala (AMG), septum (SEP), dorsal striatum (DST), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in rats following chronic nicotine exposure (0-W), 24 h withdrawal (24-W), and 48 h withdrawal (48-W). Bars represent the mean ± standard error of mean; ** p < 0.01, *** p < 0.001 (n = 7–10 per group).
Figure 6
Figure 6
Comparison of CRFR1 mRNA levels in the ventral tegmental area (VTA), medial hypothalamic area (MHA), amygdala (AMG), septum (SEP), dorsal striatum (DST), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in rats following chronic nicotine exposure (0-W), 24 h withdrawal (24-W), or 48 h withdrawal (48-W). Bars represent the mean ± standard error of mean; * p < 0.05 (n = 8–10 per group).
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