Intergenerational consequences of adolescent morphine exposure on learning and memory.

Drug addiction is a worldwide social and medical disorder. More than 50 percent of drug abusers start their substance abuse in adolescence between the ages of 15-19. Adolescence is a sensitive and crucial period for the development and maturity of the brain. Chronic exposure to morphine, particularly during this period, lead to long-lasting effects, including effects that extend to the next generation. The current study examined the intergenerational effects of paternal morphine exposure during adolescence on learning and memory. In this study, male Wistar rats were exposed to increasing doses of morphine (5-25 mg/kg, s.c.) or saline for 10 days at postnatal days (PND) 30-39 during adolescence. Following a 20-day drug-free period, the treated male rats were mated with naïve females. Adult male offspring (PND 60-80) were tested for working memory, novel object recognition memory, spatial memory, and passive avoidance memory using the Y-Maze, novel object recognition, Morris water maze, and shuttle box tests, respectively. The spontaneous alternation (as measured in the Y-Maze test) was significantly less in the morphine-sired group compared to the saline-sired one. The offspring showed significantly less discrimination index in the novel object recognition test when compared to the control group. Morphine-sired offspring tended to spend significantly more time in the target quadrant and less escape latency in the Morris water maze on probe day when compared to the saline-sired ones. The offspring showed significantly less step-through latency to enter the dark compartment compared to the control group when measured in the shuttle box test. Paternal exposure to morphine during adolescence impaired working, novel object recognition, and passive avoidance memory in male offspring. Spatial memory changed in the morphine-sired group compared to the saline-sired one.

Persistent alterations in seizure susceptibility, drug responsiveness and comorbidities associated with chemical kindling after neonatal exposure to an organophosphate.

Developmental exposure to organophosphates (OPs), at doses that do not cause cholinergic crisis, induces profound and lasting alterations in different neurotransmitter systems, which contribute to several behavioral outcomes. The present work examines whether neonatal exposure to low dose of chlorpyrifos (CPF), a widely used OP insecticide, alters the general excitability of the adult brain, its responsiveness to drugs with antiepileptic properties, the process of chemical kindling and the kindling-induced behavioral outcomes. Neonatal rats were exposed to daily doses of CPF (1 mg/kg) or dimethyl sulfoxide (DMSO, vehicle) on postnatal days (PND) 1-4. On PND 60, a subgroup of animals from both CPF and DMSO groups were injected with additive doses of pentylenetetrazole (PTZ) to evaluate the latency time to the first seizure, the threshold of PTZ-induced convulsion, and to determine the anticonvulsive action of phenobarbital (20 mg/kg), ethosuximide (100 mg/kg) and scopolamine (0.6 mg/kg) when used as pretreatment. Rats in the other subgroups were kindled by repeated intraperitoneal injections of an initially subconvulsive dose of PTZ (37.5 mg/kg) at 48-h intervals for 4 weeks. Kindled rats were then subjected to radial arm maze, sweet taste preference and forced swim test. Neonatal exposure to CPF shortened the latency time to the first seizure after pretreatment with scopolamine in female rats and decreased the threshold for PTZ-induced clonic convulsions after phenobarbital pretreatment in male rats. Neonatal CPF exposure also decreased the rate of kindling progression in female rats during early stages of PTZ kindling. On the other hand, CPF exposure sex-selectively reduced the number of working memory errors after kindling only in male rats. Drug challenge with MK-801 induced more impairment in the working memory of female kindled rats, indicating more dependence of working memory on NMDA receptor activity in these animals. Female kindled rats from CPF exposed group also showed longer time of immobility in forced swim test, showing an increase in the depressive-like behavior. This difference was also observed in the second session of forced swim test, after treating with fluoxetine, a selective inhibitor of serotonin reuptake. The recent finding, together with lack of difference in the sweet taste preference, suggests that mechanism beyond the reduction of serotonergic activity underlie the increased depressive-like behavior in this animals. To our knowledge, this is the first report describing the potential contribution of developmental exposure to an OP in susceptibility to antiepileptic drug resistance and alteration of seizure-induced behavioral deficits.

Study of the Association of Mutant HBsAg Gene and Hodgkin and Non-Hodgkin Lymphoma.

BACKGROUND: Hepatitis B Virus (HBV) is responsible for chronic, acute, and fulminant hepatitis, which are prevalent worldwide. Chronic HBV may lead to cirrhosis and hepatocellular carcinoma. Several epidemiological studies have indicated that hepatitis B virus is involved in B-cell Hodgkin and Non-Hodgkin Lymphoma (NHL). OBJECTIVES: The aim of this study was to evaluate the association between hepatitis B infection and Hodgkin and non-Hodgkin Lymphoma. MATERIALS AND METHODS: Paraffin embedded of 41 block samples including 12 (29.26%) Hodgkin and 29 (70.73%) non-Hodgkin patients were collected. Next, DNA extraction was carried out for all the samples followed by HBV DNA detection by the nested polymerase chain reaction (PCR). The positive HBV DNA samples were sequenced, and HBV genotypes and HBV subtypes were determined. RESULTS: Three out of 12 (25%) Hodgkin samples and seven out of 29 (24.13%) non-Hodgkin showed positive HBV DNA results. The results of sequencing revealed that the D genotype was predominant among the positive HBV patients. Interestingly an unpredictable amino acid proline was detected in position 88 of the HBs gene, which indicates a new mutation in the "S" region of HBV DNA in patients with Hodgkin and non-Hodgkin lymphoma. CONCLUSIONS: A high rate of 25% and 24.13% of HBV DNA was detected among patients with Hodgkin and non-Hodgkin lymphoma, respectively.