Prior work has established that acute ethanol administration causes an elevation of GABAergic neuroactive steroids in plasma and brain including 3a-hydroxy-5a-pregnan-20-one (allopregnanolone, ALLO) in Sprague Dawley rats. Over the course of several years, replications of ongoing experiments suggested that statistically significant ethanol-induced elevations in ALLO levels varied throughout the year, from 2.6 ng/g to 9.8 ng/g. To determine if this observation involved a seasonal effect on ethanol induction of ALLO homeostasis, we investigated the effect of ethanol administration (2 g/kg, i.p.) during the middle of Dec, Mar, July and Sept and measured ALLO levels in cerebral cortex. Sprague Dawley rats were acclimated to the vivarium for two weeks and maintained with a 12-hour light/dark cycle (lights on at 07:00) with ad lib access to lab chow and water. Naive rats were handled for 5 days prior to the experiment, and injected with ethanol (2 g/kg, i.p., w/v) or saline 1 hour before sacrifice. Cortical ALLO was significantly increased by acute ethanol exposure (ANOVA: F=173.3, p<0.001) during every month tested and saline-injected animals showed no significant changes throughout the year. However, there were significant differences in ethanol-induced cortical ALLO levels across the months of analysis. Ethanol-induced ALLO levels were greatest in July (6.02 ± 0.45 ng/g) and lowest in December (2.23±0.31 ng/g) with intermediate effects in March (5.13±0.42 ng/g) and Sept (4.28±0.61 ng/g). Additionally, the ALLO response to ethanol was smaller in December (146% increase vs. saline, p=0.0006), compared to other time points (Mar: 432%, p<0.0001; July: 366%, p<0.0001; Sept: 442%, p<0.0001). These results suggest that variability in ethanol-induced changes in ALLO levels may be related to seasonal regulation of neurosteroid synthesis or degradation. Future studies will determine effects on other GABAergic neuroactive steroids in plasma and other brain regions.
Seasonal variations of ethanol effects on cerebral cortical allopregnanolone levels
Porcu P;
2008
Abstract
Prior work has established that acute ethanol administration causes an elevation of GABAergic neuroactive steroids in plasma and brain including 3a-hydroxy-5a-pregnan-20-one (allopregnanolone, ALLO) in Sprague Dawley rats. Over the course of several years, replications of ongoing experiments suggested that statistically significant ethanol-induced elevations in ALLO levels varied throughout the year, from 2.6 ng/g to 9.8 ng/g. To determine if this observation involved a seasonal effect on ethanol induction of ALLO homeostasis, we investigated the effect of ethanol administration (2 g/kg, i.p.) during the middle of Dec, Mar, July and Sept and measured ALLO levels in cerebral cortex. Sprague Dawley rats were acclimated to the vivarium for two weeks and maintained with a 12-hour light/dark cycle (lights on at 07:00) with ad lib access to lab chow and water. Naive rats were handled for 5 days prior to the experiment, and injected with ethanol (2 g/kg, i.p., w/v) or saline 1 hour before sacrifice. Cortical ALLO was significantly increased by acute ethanol exposure (ANOVA: F=173.3, p<0.001) during every month tested and saline-injected animals showed no significant changes throughout the year. However, there were significant differences in ethanol-induced cortical ALLO levels across the months of analysis. Ethanol-induced ALLO levels were greatest in July (6.02 ± 0.45 ng/g) and lowest in December (2.23±0.31 ng/g) with intermediate effects in March (5.13±0.42 ng/g) and Sept (4.28±0.61 ng/g). Additionally, the ALLO response to ethanol was smaller in December (146% increase vs. saline, p=0.0006), compared to other time points (Mar: 432%, p<0.0001; July: 366%, p<0.0001; Sept: 442%, p<0.0001). These results suggest that variability in ethanol-induced changes in ALLO levels may be related to seasonal regulation of neurosteroid synthesis or degradation. Future studies will determine effects on other GABAergic neuroactive steroids in plasma and other brain regions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
