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Male Rats’ Cocaine Exposure Affects Their Male Offspring’s Drug Responses

Figure 2. Brain-Derived Neurotrophic Factor Is Increased in Male Offspring of Cocaine-Exposed Sires (A) Male rats whose sires had self-administered cocaine showed increased levels of BDNF protein in the median prefrontal cortex compared with male offspring of control sires. BDNF levels did not differ significantly between female offspring of exposed and control sires. (Bars represent the ratio of BDNF to the gene for glyceraldehyde 3-phosphate dehydrogenase (%Gapdh), which is more significant for comparisons between rats than the absolute BDNF level.) (B) Male, but not female, offspring of cocaine-exposed sires had higher levels of mRNA for BDNF that contains the noncoding exon IV. (Bars represent the ratio of BDNF mRNA to the gene for glyceraldehyde 3-phosphate dehydrogenase (%Gapdh), which is more significant for comparisons between rats than the absolute BDNF mRNA level.) (C) Increased mRNA levels were associated with increased acetylation of histone H3 at the BDNF exon IV promoter. Histone acetylation is an epigenetic mechanism that promotes gene transcription and protein production.

Brain-derived Neurotrophic Factor (BDNF) (%Gapdh)

Bar chart A shows that male offspring of cocaine-experienced rat sires had significantly higher levels of BDNF, p<0.05, compared to male offspring of control rats that received no cocaine. BDNF levels of female offspring of control rats and cocaine-experience sires were similar, and both were lower than in those of either group of male offspring. Bar chart B shows that levels of BDNF mRNA transcript were four times greater in male offspring of cocaine-experience sires than in male control rats or either group of female rats, p <0.05.

Bar chart C shows that three times as much BDNF histone 3 was acetylated in offspring of cocaine-exposed rats than in offspring of control rats, p<0.05.

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