Addiction to drugs, including opioids is the result of an interplay between environmental and genetic factors. It has been shown that the progeny of addict people is at higher risk for drug addiction. However, the mechanisms of such trans-generational effects of drugs are not so clear. Here we have evaluated the effects of parental morphine consumption on anxiety, morphine preference, and mRNA expression of dopamine receptors in F1 and F2 male offspring. Morphine was chronically administered to adult male and female Wistar rats followed by 14-day abstinence before mating. Morphine preference and anxiety-like behavior in the offspring were measured by two-bottle-choice paradigm and elevated-plus maze, respectively. Real-time PCR was used to measure the mRNA expression level of dopamine receptors in the striatum, nucleus accumbens, prefrontal cortex, and hippocampus of F1 animals. The results indicated that F1 but not the F2 male progeny of morphine-exposed parents had a greater preference for morphine, and more anxiety-like behavior compared to the offspring of saline-treated parents. In F1 male progeny of morphine-treated parents, D1 and D5 dopamine receptors were significantly increased in the prefrontal cortex and nucleus accumbens. D5 and D2 receptors were decreased in the hippocampus. D4 dopamine receptor was augmented in striatum and hippocampus and decreased in the prefrontal cortex. Adulthood exposure to chronic morphine in male and female rats before conception leads to higher morphine preference and increased anxiety in F1 but not F2 male progeny. Alterations of dopamine receptor expression in the reward system may be one mechanism responsible for observed changes in F1 offspring.

Background: The recent release of two large intracellular electrophysiological databases now allows high-dimensional systematic analysis of mechanisms of information processing in the neocortex. Here, to complement these efforts, we introduce a freely and publicly available database that provides a comparative insight into the role of various neuromodulatory transmitters in controlling neural information processing. Findings: A database of in vitro whole-cell patch-clamp recordings from primary somatosensory and motor cortices (layers 2/3) of the adult mice (2-15 months old) from both sexes is introduced. A total of 464 current-clamp experiments from identified excitatory and inhibitory neurons are provided. Experiments include recordings with (i) Step-and-Hold protocol during which the current was transiently held at 10 steps, gradually increasing in amplitude, (ii) 'Frozen Noise' injections that model the amplitude and time-varying nature of synaptic inputs to a neuron in biological networks. All experiments follow a within neuron across drug design which includes a vehicle control and a modulation of one of the following targets in the same neuron: dopamine and its receptors D1R, D2R, serotonin 5HT1f receptor, norepinephrine Alpha1, and acetylcholine M1 receptors. Conclusions: This dataset is the first to provide a systematic and comparative insight into the role of the selected neuromodulators in controlling cellular excitability. The data will help to mechanistically address how bottom-up information processing can be modulated, providing a reference for studying neural coding characteristics and revealing the contribution of neuromodulation to information processing.

Published by United Scientific GroupAbstract N-methyl-D-aspartate (NMDA) receptors are mainly involved in opioid addiction and are highly expressed in the brain reward pathway. Presence of GluN3A subunit in the composition of NMDA receptor decreases conductance of receptor channel. Opioid administration may change the expression pattern of NMDA receptor subunits. Here we have investigated the mRNA expression alterations of GluN3A subunit of the NMDA receptor in the rat brain after acute and chronic morphine administration. Male Wistar rats received chronic intraperitoneal injections of escalating doses of morphine twice daily for 6 days. Control animals received saline instead of morphine with the same protocol. Two other groups received acute single dose of morphine (30 mg/kg) or saline, respectively. The mRNA expression of GluN3A subunit of NMDA receptor in prefrontal cortex, hippocampus, striatum, and nucleus accumbens was evaluated using real-time PCR method. The mRNA expression level of GluN3A subunit was significantly increased (1.5 fold) in prefrontal cortex in chronic morphine administered rats compared to control group. No statistically significant difference was observed between control and chronic morphine treated rats in other sites of the brain. In acute morphine administered animals, no significant difference was observed in GluN3A subunit expression in evaluated sites of the brain compared to the control group. It is concluded that chronic morphine administration leads to the up-regulation of GluN3A subunit of NMDA receptor in prefrontal cortex. Involvement of this alteration in features of opioid addiction needs to be further studies in the future.