Long-term alterations in brain function following cocaine administration during the preweanling period
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D L Dow-Edwards1, L A Freed-Malen, H E Hughes
1Department of Pharmacology, State University of New York, Brooklyn 11203.
Insights
Early cocaine exposure (postnatal days 11-20) significantly impacts long-term brain metabolism in female rats more than males. This study reveals sex-specific metabolic alterations in neuronal systems following developmental cocaine exposure.
Area of Science:
- Neuroscience
- Developmental Toxicology
- Neuropharmacology
Background:
- Prenatal and early postnatal exposure to drugs of abuse can lead to long-term neurodevelopmental deficits.
- Previous research has indicated that cocaine exposure during early postnatal development (P 1-10) affects neuronal metabolism.
- Understanding the sex-specific effects of cocaine exposure during critical developmental windows is crucial for assessing long-term health risks.
Purpose of the Study:
- To investigate the long-term consequences of cocaine exposure during a specific postnatal developmental period (days 11-20) on cerebral glucose metabolism.
- To compare the metabolic effects of cocaine exposure between male and female rats.
- To differentiate the metabolic outcomes from those previously observed with earlier cocaine exposure (P 1-10).
Main Methods:
- Rat pups were administered cocaine (50mg/kg) or vehicle subcutaneously during postnatal days 11-20.
- Cerebral glucose metabolic patterns were assessed in adult rats (60-64 days of age) using [specify method if known, e.g., Positron Emission Tomography (PET) or 2-deoxy-2-[18F]fluoro-D-glucose (FDG) autoradiography].
- Metabolic rates in various brain structures, including motor, limbic, and sensory systems, were quantified and compared between sexes and treatment groups.
Main Results:
- Female rats exposed to cocaine during P 11-20 exhibited increased metabolic rates in 18 out of 46 evaluated brain structures, notably in motor (5/6) and limbic (7/17) systems.
- No decreased metabolic rates were observed in cocaine-exposed females.
- Male rats showed no significant metabolic changes in motor structures or hypothalamus; however, decreased glucose utilization was noted in 2/17 limbic structures, and increased rates in 2/11 sensory structures.
Conclusions:
- Postnatal cocaine exposure during days 11-20 induces significant and lasting alterations in cerebral glucose metabolism, with females exhibiting more pronounced effects than males.
- The observed metabolic changes are sex-dependent and differ from those resulting from cocaine exposure during an earlier developmental window (P 1-10).
- These findings highlight the critical role of developmental timing and sex in mediating the long-term neurobiological consequences of early-life cocaine exposure.
Abstract:
This report examines the long-term effects of cocaine exposure during postnatal days (P) 11-20 on the metabolic function of major central neuronal systems. Cocaine (50mg/kg) or vehicle was administered subcutaneously to rat pups during P 11-20. At 60-64 days of age, the rats were examined for cerebral glucose metabolic patterns. In cocaine-treated females 18 of the 46 structures evaluated showed increased metabolic rates including 5 of 6 structures within the motor system and 7 of 17 limbic structures. No decreased rates were seen. In males, cocaine had no effects in the motor structures or hypothalamus while 2 of 17 structures within the limbic system showed decreased rates of glucose utilization and 2 of 11 structures within the sensory systems showed increased rates. These results indicate that female rats show greater long-term metabolic effects than males and that cocaine exposure during P 11-20 produces different metabolic effects than cocaine exposure during P 1-10 which we previously reported.