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Enhanced functional connectivity involving the ventromedial hypothalamus following methamphetamine exposure.

Zuloaga DG, Iancu OD, Weber S, Etzel D, Marzulla T, Stewart B, Allen CN, Raber J - Front Neurosci (2015)

Bottom Line: MA phase shifts, entrains the circadian clock and can also alter the entraining effect of light by currently unknown mechanisms.There were five distinct patterns of neuronal activation.Functional connectivity between the ventromedial hypothalamus (VMH) and other brain areas, including the paraventricular nucleus of the hypothalamus and basolateral and medial amygdala, was enhanced following MA exposure, suggesting a role for the VMH in the effects of MA on the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University Portland Portland, OR, USA ; Department of Psychology, University at Albany Albany, NY, USA.

ABSTRACT
Methamphetamine (MA) consumption causes disruption of many biological rhythms including the sleep-wake cycle. This circadian effect is seen shortly following MA exposure and later in life following developmental MA exposure. MA phase shifts, entrains the circadian clock and can also alter the entraining effect of light by currently unknown mechanisms. We analyzed and compared immunoreactivity of the immediate early gene c-Fos, a marker of neuronal activity, to assess neuronal activation 2 h following MA exposure in the light and dark phases. We used network analyses of correlation patterns derived from global brain immunoreactivity patterns of c-Fos, to infer functional connectivity between brain regions. There were five distinct patterns of neuronal activation. In several brain areas, neuronal activation following exposure to MA was stronger in the light than the dark phase, highlighting the importance of considering circadian periods of increased effects of MA in defining experimental conditions and understanding the mechanisms underlying detrimental effects of MA exposure to brain function. Functional connectivity between the ventromedial hypothalamus (VMH) and other brain areas, including the paraventricular nucleus of the hypothalamus and basolateral and medial amygdala, was enhanced following MA exposure, suggesting a role for the VMH in the effects of MA on the brain.

No MeSH data available.


Related in: MedlinePlus

Brain areas that showed effects of treatment and a treatment × time interaction. The increase in the number of c-Fos positive cells following MA exposure is greater in the day than in the night in the PVN (A), PVT (B), and ARC (C). In these three brain regions there was a MA × time interaction. In the dark phase, the number of c-Fos positive cells was only higher following MA than saline exposure in the PVT (p = 0.028) but not in the PVN or ARC. In the PVN (p < 0.0001), PVT (p = 0.01), and ARC (p = 0.03) neuronal activation following MA exposure was significantly greater in the light than dark phase. In contrast, in the ARC, neuronal activation following MA exposure was significantly greater in the dark than the light phase (p < 0.01). In the PVN (p = 0.12) and PVT (p = 0.20), there was no difference in neuronal activation following saline exposure in the light and dark phase. Representative images for neuronal activation in the PVN following saline or MA exposure in the day and night are shown in (D). n = 10 mice/treatment/time period.
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Figure 3: Brain areas that showed effects of treatment and a treatment × time interaction. The increase in the number of c-Fos positive cells following MA exposure is greater in the day than in the night in the PVN (A), PVT (B), and ARC (C). In these three brain regions there was a MA × time interaction. In the dark phase, the number of c-Fos positive cells was only higher following MA than saline exposure in the PVT (p = 0.028) but not in the PVN or ARC. In the PVN (p < 0.0001), PVT (p = 0.01), and ARC (p = 0.03) neuronal activation following MA exposure was significantly greater in the light than dark phase. In contrast, in the ARC, neuronal activation following MA exposure was significantly greater in the dark than the light phase (p < 0.01). In the PVN (p = 0.12) and PVT (p = 0.20), there was no difference in neuronal activation following saline exposure in the light and dark phase. Representative images for neuronal activation in the PVN following saline or MA exposure in the day and night are shown in (D). n = 10 mice/treatment/time period.

Mentions: Some regions showed only a profound increase in c-Fos positive cells following MA in the day. A significant interaction between treatment and time was found in the PVN [F(1, 36) = 26.51, p < 0.001; Figure 3A], PVT [F(1, 36) = 9.26, p < 0.01; Figure 3B], and ARC [F(1, 36) = 90.17, p < 0.001; Figure 3C]. In the light phase, the number of c-Fos positive cells was higher following MA than saline exposure in the PVN (p < 0.001), PVT (p < 0.001), and ARC (p < 0.001). In the dark phase, the number of c-Fos positive cells was only higher following MA than saline exposure in the PVT (p = 0.028) but not in the PVN or ARC. In the PVN, in addition to the MA × time interaction, there were also main effects of MA [F(1, 36) = 38.09, p < 0.001] and time [F(1, 36) = 12.89, p < 0.001; Figure 3A). Representative images for neuronal activation in the PVN following saline or MA exposure in the light and dark phases are shown in Figure 3D. In addition to the MA × time interaction, there were also main effects of MA in the PVT [F(1, 36) = 50.24, p < 0.001; Figure 2B], and ARC [F(1, 36) = 15.05, p < 0.001; Figure 2C]. As there was a treatment × time interaction in these brain areas, we also assessed whether for each treatment there was a significant difference between neuronal activation in the light and dark phase. In the PVN (p < 0.0001), PVT (p = 0.01), and ARC (p = 0.03) neuronal activation following MA exposure was significantly greater in the light than dark phase. In contrast, in the ARC, neuronal activation following saline exposure was significantly greater in the dark than the light phase (p < 0.01). In the PVN (p = 0.12) and PVT (p = 0.20), there was no difference in neuronal activation following saline exposure in the light and dark phase.


Enhanced functional connectivity involving the ventromedial hypothalamus following methamphetamine exposure.

Zuloaga DG, Iancu OD, Weber S, Etzel D, Marzulla T, Stewart B, Allen CN, Raber J - Front Neurosci (2015)

Brain areas that showed effects of treatment and a treatment × time interaction. The increase in the number of c-Fos positive cells following MA exposure is greater in the day than in the night in the PVN (A), PVT (B), and ARC (C). In these three brain regions there was a MA × time interaction. In the dark phase, the number of c-Fos positive cells was only higher following MA than saline exposure in the PVT (p = 0.028) but not in the PVN or ARC. In the PVN (p < 0.0001), PVT (p = 0.01), and ARC (p = 0.03) neuronal activation following MA exposure was significantly greater in the light than dark phase. In contrast, in the ARC, neuronal activation following MA exposure was significantly greater in the dark than the light phase (p < 0.01). In the PVN (p = 0.12) and PVT (p = 0.20), there was no difference in neuronal activation following saline exposure in the light and dark phase. Representative images for neuronal activation in the PVN following saline or MA exposure in the day and night are shown in (D). n = 10 mice/treatment/time period.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 3: Brain areas that showed effects of treatment and a treatment × time interaction. The increase in the number of c-Fos positive cells following MA exposure is greater in the day than in the night in the PVN (A), PVT (B), and ARC (C). In these three brain regions there was a MA × time interaction. In the dark phase, the number of c-Fos positive cells was only higher following MA than saline exposure in the PVT (p = 0.028) but not in the PVN or ARC. In the PVN (p < 0.0001), PVT (p = 0.01), and ARC (p = 0.03) neuronal activation following MA exposure was significantly greater in the light than dark phase. In contrast, in the ARC, neuronal activation following MA exposure was significantly greater in the dark than the light phase (p < 0.01). In the PVN (p = 0.12) and PVT (p = 0.20), there was no difference in neuronal activation following saline exposure in the light and dark phase. Representative images for neuronal activation in the PVN following saline or MA exposure in the day and night are shown in (D). n = 10 mice/treatment/time period.
Mentions: Some regions showed only a profound increase in c-Fos positive cells following MA in the day. A significant interaction between treatment and time was found in the PVN [F(1, 36) = 26.51, p < 0.001; Figure 3A], PVT [F(1, 36) = 9.26, p < 0.01; Figure 3B], and ARC [F(1, 36) = 90.17, p < 0.001; Figure 3C]. In the light phase, the number of c-Fos positive cells was higher following MA than saline exposure in the PVN (p < 0.001), PVT (p < 0.001), and ARC (p < 0.001). In the dark phase, the number of c-Fos positive cells was only higher following MA than saline exposure in the PVT (p = 0.028) but not in the PVN or ARC. In the PVN, in addition to the MA × time interaction, there were also main effects of MA [F(1, 36) = 38.09, p < 0.001] and time [F(1, 36) = 12.89, p < 0.001; Figure 3A). Representative images for neuronal activation in the PVN following saline or MA exposure in the light and dark phases are shown in Figure 3D. In addition to the MA × time interaction, there were also main effects of MA in the PVT [F(1, 36) = 50.24, p < 0.001; Figure 2B], and ARC [F(1, 36) = 15.05, p < 0.001; Figure 2C]. As there was a treatment × time interaction in these brain areas, we also assessed whether for each treatment there was a significant difference between neuronal activation in the light and dark phase. In the PVN (p < 0.0001), PVT (p = 0.01), and ARC (p = 0.03) neuronal activation following MA exposure was significantly greater in the light than dark phase. In contrast, in the ARC, neuronal activation following saline exposure was significantly greater in the dark than the light phase (p < 0.01). In the PVN (p = 0.12) and PVT (p = 0.20), there was no difference in neuronal activation following saline exposure in the light and dark phase.

Bottom Line: MA phase shifts, entrains the circadian clock and can also alter the entraining effect of light by currently unknown mechanisms.There were five distinct patterns of neuronal activation.Functional connectivity between the ventromedial hypothalamus (VMH) and other brain areas, including the paraventricular nucleus of the hypothalamus and basolateral and medial amygdala, was enhanced following MA exposure, suggesting a role for the VMH in the effects of MA on the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University Portland Portland, OR, USA ; Department of Psychology, University at Albany Albany, NY, USA.

ABSTRACT
Methamphetamine (MA) consumption causes disruption of many biological rhythms including the sleep-wake cycle. This circadian effect is seen shortly following MA exposure and later in life following developmental MA exposure. MA phase shifts, entrains the circadian clock and can also alter the entraining effect of light by currently unknown mechanisms. We analyzed and compared immunoreactivity of the immediate early gene c-Fos, a marker of neuronal activity, to assess neuronal activation 2 h following MA exposure in the light and dark phases. We used network analyses of correlation patterns derived from global brain immunoreactivity patterns of c-Fos, to infer functional connectivity between brain regions. There were five distinct patterns of neuronal activation. In several brain areas, neuronal activation following exposure to MA was stronger in the light than the dark phase, highlighting the importance of considering circadian periods of increased effects of MA in defining experimental conditions and understanding the mechanisms underlying detrimental effects of MA exposure to brain function. Functional connectivity between the ventromedial hypothalamus (VMH) and other brain areas, including the paraventricular nucleus of the hypothalamus and basolateral and medial amygdala, was enhanced following MA exposure, suggesting a role for the VMH in the effects of MA on the brain.

No MeSH data available.


Related in: MedlinePlus