Investigating Facilitatory Effects of Lithium on Methamphetamine-induced Spatial Memory Impairments in Rat.

Introduction: It has long been known that Methamphetamine (MA), as a psychostimulant, leads to long-lasting cognitive deficits. Previous studies have shown that lithium, a mood stabilizer, could facilitate cognitive ability in most of brain diseases. In current study the effects of lithium on spatial memory, hippocampal apoptosis and brain edema in METH-exposed rats are investigated. Methods: The present study 32 Wistar rats were used to examine the effects of lithium on spatial memory by the Morris water maze, hippocampal apoptosis using the TUNEL assay, and brain edema following MA administrations. Results: The findings indicated that treatment with lithium significantly ameliorated spatial learning and memory impairment in MA-treated rats. In addition, the findings showed that treatment with lithium significantly reduced brain edema and apoptosis in the CA1 neurons in MA -exposed rats. Conclusion: The results show that treatment with lithium can partially ameliorate the MA-induced neurocognitive deficits in rats, which may be related to its protective effect in the hippocampus.

Transgenerational influence of parental morphine exposure on pain perception, anxiety-like behavior and passive avoidance memory among male and female offspring of Wistar rats.

Accumulating evidence suggests that epigenetic mechanisms play an important role in the formation and maintenance of memory within the brain. Moreover, the effect of parental drug-exposure before gestation on behavioral state of offspring has been little studied. The main objective of the current study is to evaluate the effect of parental morphine exposure on avoidance memory, morphine preference and anxiety-like behavior of offspring. The total of 32 males and 32 females were used for mating. The animals were treated with morphine. The offspring according to their parental morphine treatment was divided into four groups (n=16) including paternally treated, maternally treated, both of parents treated and naïve animals. The pain perception, anxiety-like behavior, and avoidance memory were evaluated in the offspring. In the current study, the total of 256 offspring was used for the experiments (4 tasks × 4 groups of offspring × 8 female offspring × 8 male offspring). The finding revealed that the avoidance memory and visceral pain were reduced significantly in male and female offspring with at least one morphine-treated parent. Moreover, anxiety-like behavior was reduced significantly in the male offspring with at least one morphine-treated parent. While anxiety-like behavior was increased significantly in female offspring that were treated by morphine either maternally or both of parents. The data revealed that the endogenous opioid system may be altered in the offspring of morphine-treated parent(s), and epigenetic role could be important. However, analysis of variance signified the important role of maternal inheritance.

µ-Opioid receptor in the CA1 involves in tramadol and morphine cross state-dependent memory.

In the present study, the effect of tramadol - an opioid painkiller drug with abuse potential- on amnesia and state-dependent memory and its interaction with the opioidergic system was investigated in male Wistar rats. Intra CA-1 administration of tramadol (0.5, 1, and 2 µg/rat) before training, dose-dependently decreased the learning ability in passive avoidance task. Amnesia induced by pre-train tramadol administration was significantly reversed by pre-test administration of tramadol (1 µg/rat). Pre-test administration of naltrexone (a µ-opioid receptor (MOR) antagonist) inhibited the effect of tramadol on memory retrieval. In addition, the pre-test administration of morphine (1 µg/rat, intra-CA1) also reversed memory impairment induced by pre-train tramadol administration. Although, pre-train morphine administration (1 µg/rat, intra-CA1), induced memory impairment reversed by pre-test tramadol administration (1 µg/rat, intra-CA1). In addition, the level of MOR in the hippocampus decreased in animals with memory impairment due to using tramadol in the training day. However, state-dependent retrieval using tramadol or cross state-dependent retrieval using morphine enhanced the MOR level in the hippocampus. The results of the study suggested that intra-CA1 tramadol administration induced memory impairment, improved by pre-test administration of either tramadol or morphine (MOR agonist). It could be concluded that tramadol is capable to induced state-dependent memory and also, it has a cross state-dependent memory with morphine in the hippocampus, done possibly through MOR.

Correlation among the Behavioral Features in the Offspring of Morphine-Abstinent Rats.

BACKGROUND: Critical analysis of new evidence in medical sciences relies on statistics in terms of correlation. The aim of the present study was to evaluate the correlation coefficients among the behavioral features in the offspring of morphine-abstinent parent(s). METHODS: The offspring of rats with various parental morphine-exposure were divided into four groups including offspring with healthy parents (CTL), offspring with paternal morphine-abstinent (PMA) parent, offspring with maternal morphine-abstinent (MMA) parent, and offspring with both morphine-abstinent (BMA) parents. Pain perception, depression-like behavior and avoidance-memory in the offspring were quantified. The association between variables was measured using Pearson correlation analysis. FINDINGS: A strong correlation was observed between pain and depressive-like behavior in female and male offspring of healthy parents. Moreover, in the male and female offspring of healthy parents and BMA, no significant correlation was observed between avoidance memory and pain behavior or depressive-like behavior. However, in the offspring of MMA, a strong correlation was observed between avoidance memory and depressive-like behavior. CONCLUSION: The results revealed that in comparison with the offspring with CTL, the correlation among the behavioral futures in the offspring with MMA or PMA parents is significantly different.

Effect of rat parental morphine exposure on passive avoidance memory and morphine conditioned place preference in male offspring.

Drug addiction is a chronic disorder resulted from complex interaction of genetic, environmental, and developmental factors. Epigenetic mechanisms play an important role in the development and maintenance of addiction and also memory formation in the brain. We have examined passive avoidance memory and morphine conditioned place preference (CPP) in the offspring of male and/or female rats with a history of adulthood morphine consumption. Adult male and female animals received chronic oral morphine for 21days and then were maintained drug free for 10days. After that, they were let to mate with either an abstinent or control rat. Male offspring's memory was evaluated by step through test. Besides, rewarding effects of morphine were checked with CCP paradigm. Offspring of abstinent animals showed significant memory impairment compared to the control group which was more prominent in the offspring of abstinent females. Conditioning results showed that administration of a high dose of morphine (10mg/kg) that could significantly induce CPP in control rats, was not able to induce similar results in the offspring of morphine abstinent parents; and CPP was much more prominent when it was induced in the offspring of morphine exposed females compared to the progeny of morphine exposed males. It is concluded that parental morphine consumption in adulthood even before mating has destructive effects on memory state of the male offspring and also leads to tolerance to the rewarding effects of morphine. These effects are greater when the morphine consumer parent is the female one.