The effects of kindling during pregnancy on long-term potentiation (LTP) induction and M1 muscarinic acetylcholine receptors in male rat offspring.

Background and purpose: Neonates of pregnant women with epilepsy may compromise normal neurodevelopment and hippocampal morphology. Memory and learning disorders and a decrease in verbal IQ scores are seen in these children later in life. In the previous study, we suggested that the central muscarinic cholinergic receptors had an important role in learning and memory deficits induced by prenatal pentylenetetrazol-kindling in pups born to kindled mothers. This study aimed to investigate the effects of kindling during pregnancy on long-term potentiation (LTP) induction and the role of M1 muscarinic acetylcholine receptors in the hippocampus of male offspring. Experimental approach: Twenty female Wistar rats were divided into two groups on the 13th day of their gestation (kindled and control; n = 10). Animals in the first group were kindled by i.p. injections of 25 mg/kg body weight pentylenetetrazol every 15 min until seizures occurred and the control group received normal saline. The effect of maternal seizures and perfusion of specific M1 muscarinic receptors antagonist (telenzepine at doses of 0.01, 0.1, and 1 nmol) on the LTP induction of 80 pups were tested at 12 weeks of age by field potential recordings. Findings/Results: The results of the electrophysiological study revealed that recurrent seizures during pregnancy impaired field excitatory postsynaptic potentials (fEPSP)-LTP induction and normal development of M1 muscarinic receptors in the hippocampus of male offspring. Also, the results demonstrated that maternal seizure did not significantly affect the paired-pulse indexes and population spike-LTP in the hippocampus of male offspring. Conclusion and implications: Our study showed that recurrent seizures during pregnancy cause impaired fEPSP-LTP induction and abnormal development of the M1 muscarinic receptor in the hippocampus.

Adolescent morphine exposure impairs dark avoidance memory and synaptic potentiation of ventral hippocampal CA1 during adulthood in rats.

Adolescence is a neurobiological critical period for neurodevelopmental processes. Adolescent opioid exposure can affect cognitive abilities via regional-specific lasting changes in brain structure and function. The current study was therefore designed to assess the long-term effects of adolescent morphine exposure on dark avoidance memory and synaptic plasticity of the ventral hippocampal CA1. Adolescent Wistar rats received escalating doses of morphine for 10 days. Morphine injections were started with an incremental dose of 2.5 mg/kg to reach a dose of 25 mg/kg. 30 days after the last injection, inhibitory memory and in vitro field potential recording were evaluated. Also, the weight of the animals was measured during drug and post-drug exposure. We found that adolescent morphine exposure decreased weight gain during morphine and post-morphine exposure. Passive avoidance memory was impaired in the morphine group. Moreover, adolescent morphine exposure caused an increase in baseline synaptic responsiveness and failed long-term potentiation (LTP) in the ventral hippocampal CA1 during adulthood. In the morphine group, the mean values of the field excitatory postsynaptic potential (fEPSP) slopes required to elicit a half-maximal population spike (PS) amplitude were significantly greater than that of the saline group. Therefore, adolescent morphine exposure has a durable effect on memory functions, synaptic activity, and plasticity of ventral hippocampal CA1. Adults with adolescent morphine exposures may experience maladaptive behaviors and cognitive disabilities.

Nandrolone administration abolishes hippocampal fEPSP-PS potentiation and passive avoidance learning of adolescent male rats.

Despite the chronic effects of nandrolone decanoate (ND), the acute effects of ND on passive avoidance learning (PAL) and memory and its mechanism have not been investigated. This research examines the acute effect of ND on PAL, CA1 synaptic plasticity, testosterone and corticosterone serum levels, and the role of androgenic receptors (ARs). Adolescent male rats were treated with ND, 30 min before training and retention and after training test. AR antagonist was applied 15 min before ND. Hippocampal slices were perfused by ND. ND administration had an inverted U-shape effect on acquisition of PAL and on testosterone and corticosterone serum levels. The consolidation was only affected by high dose of ND. ND significantly decreased the retention of PAL across all doses. The magnitude of field excitatory postsynaptic potential long term potentiation was lower than that of control slices. In addition, an attenuation of field excitatory postsynaptic potential population spike coupling was also observed. Nilutamide could nullify the ND impairment effect. We concluded although a single dose of ND could affect all stages of PAL, its effects were more potent on retrieval, possibly arising from the acute effect of ND on the alterations of CA1 synaptic plasticity. In addition, ND may induce its effects directly through ARs and indirectly through plasma testosterone and corticosterone.