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Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute
Jin Hee Cho1, Yun Ha Cho1, Hyo Young Kim1
1Department of Pharmacology, Korea University College of Medicine, Anam-Dong, Sungbuk-Gu, Seoul, Republic of Korea.
Abstract:
Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration.
Insights
Acute caffeine intake selectively increases cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in specific mouse brain regions. This effect is dose-dependent and transient, highlighting CART
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Caffeine's behavioral effects are primarily linked to adenosine receptor antagonism.
- The role of other neural substrates, like cocaine- and amphetamine-regulated transcript (CART), in caffeine's effects remains less understood.
- Previous research indicated repeated caffeine administration elevates CART in the mouse striatum.
Purpose of the Study:
- To investigate the acute effects of caffeine on CART immunoreactivity (CART-IR) in various mouse brain regions.
- To determine the dose- and time-dependent changes in CART-IR following a single caffeine administration.
Main Methods:
- Mice were administered a single dose of caffeine (25, 50, or 100 mg/kg).
- CART-IR was measured at different time points (2 and 8 hours post-administration).
- Immunoreactivity was assessed in specific brain areas including the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC).
Main Results:
- A high dose of caffeine (100 mg/kg) significantly increased CART-IR in the AcbSh, dBNST, CeA, PVN, Arc, and LC at 2 hours, returning to baseline by 8 hours.
- This caffeine-induced increase in CART-IR was not observed in other brain areas.
- Lower doses (25 and 50 mg/kg) also showed dose-dependent increases in CART-IR in these regions, with the 50 mg/kg dose yielding effects similar to or greater than 100 mg/kg.
Conclusions:
- Acute caffeine administration selectively modulates CART-IR in specific brain regions involved in reward, stress, and arousal.
- The observed changes in CART-IR are dose- and time-dependent, suggesting a specific neurobiological pathway affected by caffeine.
- These findings contribute to understanding the complex neural mechanisms underlying caffeine's diverse behavioral effects.
