Regional Fos expression induced by morphine withdrawal in the 7-day-old rat
Anika A McPhie1, Gordon A Barr
1Department of Psychology, Hunter College and the Graduate Center, City University of New York, New York, NY 10016, USA.
Insights
Infant rats exposed to chronic morphine show brain changes similar to adults during opiate withdrawal. This study identifies key brain regions that become metabolically active during withdrawal in developing mammals.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Human infants can experience chronic opiate exposure.
- Mechanisms of opiate dependence in infants are not well understood.
- Opiate withdrawal in adults involves specific brain regions.
Purpose of the Study:
- To investigate metabolic activity in infant rat brains during morphine withdrawal.
- To compare neural circuits involved in infant and adult opiate withdrawal.
- To determine if brain regions active in adult withdrawal are also active in infants.
Main Methods:
- Chronic morphine or saline administration to 7-day-old rat pups.
- Precipitation of withdrawal using the opiate antagonist naltrexone.
- Quantification of Fos-like immunoreactivity in select brain regions.
Main Results:
- Increased Fos-like labeled cells were observed in the periaqueductal gray, nucleus accumbens, locus coeruleus, and spinal cord.
- These findings indicate metabolic activation in these specific brain areas during withdrawal.
- The pattern of activation suggests conserved neural pathways between infant and adult withdrawal.
Conclusions:
- Neural circuits for physical opiate withdrawal are similar in infant and adult rats.
- Developing brains exhibit comparable responses to opiate withdrawal as adult brains.
- This research provides insights into the neurobiology of neonatal opiate abstinence syndrome.
Abstract:
Human infants are often exposed to opiates chronically but the mechanisms by which opiates induce dependence in the infant are not well studied. In the adult the brain regions involved in the physical signs of opiate withdrawal include the periaqueductal gray area, the locus coeruleus, amygdala, ventral tegmental area, nucleus accumbens, hypothalamus, and spinal cord. Microinjection studies show that many of these brain regions are involved in opiate withdrawal in the infant rat. Our goal here was to determine if these regions become metabolically active during physical withdrawal from morphine in the infant rat as they do in the adult. Following chronic morphine or saline treatment, withdrawal was precipitated in 7-day-old pups with the opiate antagonist naltrexone. Cells positive for Fos-like immunoreactivity were quantified within select brain regions. Increased Fos-like labeled cells were found in the periaqueductal gray, nucleus accumbens, locus coeruleus, and spinal cord. These are consistent with other studies showing that the neural circuits underlying the physical signs of opiate withdrawal are similar in the infant and adult.
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