Impaired in vivo synaptic plasticity in dentate gyrus and spatial memory in juvenile rats induced by prenatal morphine exposure

Abstract

ABSTRACT:Prenatal morphine exposure induces neurobiological changes, including deficits in learning and memory, in juvenile rat offspring. However the effects of this exposure on hippocampal plasticity, which is critical for learning and memory processes, are not well understood. The present study investigates the alterations of spatial memory and in vivo hippocampal synaptic plasticity in juvenile rats prenatally exposed to morphine. On gestation days 11-18, pregnant rats were randomly chosen to be injected twice daily with morphine or saline. Each juvenile offspring (postnatal day 22-31) performed one two-trial Y-maze task to evaluate spatial memory. Afterwards, the in vivo field excitatory postsynaptic potential (fEPSP) and population spike (PS) were recorded in the perforant path dentate gyrus (DG) pathway in the hippocampus. Prenatal morphine exposure reduced depotentiation (DP), but not longterm potentiation (LTP), of the EPSP slope. However, both LTP and DP of the EPSP slope were depressed in prenatal morphine-exposed juvenile offspring. The morphine group also showed poorer performance for the Y-maze task than the control group. Depressed PS LTP, but not EPSP LTP, in the morphine group suggested that prenatal morphine exposure changed GABAergic inhibition, which mediates EPSP-spike potentiation. Then a loss of GABA-containing neurons in the DG area of the morphine group was observed using immunohistochemistry. Taken together, our results suggest that prenatal morphine exposure impairs the juvenile offspring's dentate synaptic plasticity and spatial memory, and that decreased GABAergic inhibition may play a role in these effects. These findings might contribute to an explanation for the cognitive deficits in children whose mothers abuse opiates during pregnancy. V V C 2008 WileyLiss, Inc.

Progress in neural plasticity

“…Further studies [48] showed that the expression of SNAP-25, a SNARE protein essential for synaptic vesicle exocytosis, was regulated in the hippocampus after chronic morphine treatment, with a reduction in the formation of a ternary complex of SNARE proteins in hippocampal synaptosomes. More recently, Zhou and his colleagues [49] at the University of Science and Technology of China (USTC) in Hefei reported that prenatal morphine exposure resulted in the alteration of persistent potentiation of the population spike amplitude, but not in the LTP of perforant-dentate gyrus (DG) synapses in vivo, and such enhanced EPSPspike potentiation was attributed to the decreased inhibition caused by a loss of GABAergic neurons in the DG region of juvenile rat offspring (postnatal day [22][23][24][25][26][27][28][29][30][31]. This finding showed additional cellular mechanisms underlying the impaired spatial learning and memory in rat offspring prenatally exposed to morphine, in addition to the known mechanism associated with the reduction of hippocampal LTD and the depotentiation of LTP in the offspring [50].…”

Anesthesia and Apoptosis in the Developing Brain: An Update

“…Foetal and neonatal exposure to opioids, and in particular chronic exposure to opioids, have been associated with a variety of neuronal changes [20]. There are very few, if any, studies that have specifically examined whether or not short exposure to opioids results in apoptosis.…”

Effects of fentanyl on pain and motor behaviors following a collagenase-induced intracerebral hemorrhage in rats

“…Therefore, the decreased performance on the last 2 days for 10 µg/kg group could be explained by a functional interference of the drug. Morphine, another opioid agonist, has been shown to hinder the restructuration of new brain synapses 30. Cognitive deficits could be caused by a change of the gamma-aminobutyric acid-ergic (GABAergic) inhibition that controls neuronal excitation.…”