Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training

Abstract

Prenatal exposure to opiates, which is invariably followed by postnatal withdrawal, can affect cognitive performance. To further characterize these effects, we examined radial 8-arm maze performance and expression of brain derived neurotrophic factor (BDNF) in male rats prenatally exposed to the opiate l-α-acetylmethadol (LAAM). Female rats received 1.0 mg/kg/day LAAM or water via daily oral gavage for 28 days prior to breeding, during breeding, and throughout pregnancy. Pups were fostered to non-treated lactating dams at birth and underwent neonatal opiate withdrawal. At 5-6 months, prenatal water-and LAAM-exposed males (n=6 each; non-littermates) received radial arm maze training consisting of ten trials a day for five days and three retention trials on day six. Rats prenatally exposed to LAAM had poorer maze performance, decreased percent correct responding and more reference and working memory errors than prenatal water-treated controls. However, they were able to acquire the task by the end of training. There were no differences between the groups on retention 24 hr after testing. Following retention testing, hippocampi were removed and protein extracted from cytosol and synaptic fractions. Western blots were used to measure levels of mature and precursor BDNF protein, as well as the BDNF receptor TrkB. BDNF precursor protein was significantly decreased in the synaptic fraction of trained prenatal LAAM-treated rats compared to prenatal water-treated trained controls. No effects were found for the full-length or truncated TrkB receptor. In untrained rats, prenatal treatment did not affect any of the measures. These data suggest that prenatal opiate exposure and/or postnatal withdrawal compromise expression of proteins involved in the neural plasticity underlying learning.

Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

“…Animal studies also suggested that the learning ability and cognitive abilities were reduced in offsprings prenatally exposed to heroin,31,38 morphine,31,39 L-alpha-acetylmethadol,40 or methadone 41–43. The current study also revealed that cognitive function of offsprings was impaired after prenatal buprenorphine exposure, suggesting that prenatal exposure to different types of opioids might interfere with learning abilities and memory formation through their common site of action in the opioid system.…”

Neonatal Morphine Exposure in Very Preterm Infants—Cerebral Development and Outcomes

“…10 These alterations were often accompanied by behavioral changes. Rats exposed prenatally to a long-acting opiate demonstrated more reference and working memory errors in the radial arm maze 11 , and postnatal morphine exposure impaired reward-mediated learning in adulthood. 12 …”

Prenatal oxycodone exposure impairs spatial learning and/or memory in rats

“…The development of the prenatal oxycodone treatment paradigm is described in detail in [28]. Nulliparous female (64–70 days of age) Sprague-Dawley rats (Harlan, Indianapolis, IN) were treated with oxycodone HCl (Mallinckrodt, St. Louis, MO) or the water vehicle.…”

“…Therefore, we developed a model in which prenatal opiates are administered before and during the entire gestational period. Previous work in our laboratory using this approach with prenatal exposure to LAAM found poor performance in acquisition of the radial arm maze, a spatial memory task [28]. Prenatal LAAM-exposed rats had more reference and working memory errors, but were able to acquire the task after five days of training.…”