Effects of Nicotine Administration in an Enriched Environment on the Behavior of Male MK-801-Exposed Rats.

Background: Smoking is more common in patients with schizophrenia than in healthy populations. Some controversial hypotheses connect the disease with the high prevalence of smoking. Moreover, environmental factors affect the severity of the positive and negative symptoms of schizophrenia. The current study aimed to assess the effect of enriched environment (EE) and nicotine on the MK-801 animal model of schizophrenia. Methods: Male Wistar rat pups randomly received saline or MK-801 (dose:1 mg/kg) for five days from the sixth postnatal day (P) until the tenth. The pups were placed in EE or standard cages (SCs) after weaning (P21). Morris water maze (MWM) was used to assess spatial learning and memory. The rats received 0.6 mg/kg nicotine twice for three days at the end of the second month and were examined in an open-field box and three-chamber social interaction test. Findings: MK-801 rats' behaviors were the same as those of the saline rats when they were exposed to nicotine. No positive effects of EE were observed when the animals were exposed to nicotine. Conclusion: The results suggested that nicotine decreased schizophrenia-like symptoms and covered the positive effects of EE.

Nicotine-conditioned place preference, reversal learning and social interaction in MK-801-induced schizophrenia model: Effects of post-weaning enriched environment.

Based on the clinical observations of severe cognitive deficits in schizophrenia patients and the relationship between environmental parameters and the severity of schizophrenia symptoms, the present study investigated these parameters in an dizocilpine (MK-801)-induced schizophrenia model in rats. In addition to, it evaluated whether a post-weaning enriched environment (EE) would affect the nicotine-induced conditioned place preference (CPP) and the motor and cognitive deficits caused by MK-801 treatment. Male Wistar rat pups were injected peritoneally with MK-801 (1 mg/kg) on a daily basis between the 6th and the 10th postnatal days (P) and were exposed to either an enriched or a standard cage from P21 until the end of the experiments. The rats were evaluated in open-field and three-chamber social interaction tests. Moreover, spatial and reversal learning was assessed by the Morris water maze (MWM). The animals were conditioned with 0.6 mg/kg nicotine and tested for CPP. Increased self-grooming, exploratory behaviour, potentiated nicotine-CPP and decreased social behaviours, delayed spatial learning and memory and impaired reversal learning in the water maze were observed in the MK-801 treatment group. Housing in an EE improved cognitive and behavioural deficits associated with postnatal MK-801 treatment. The results suggested that neonatal N-methyl-d-aspartate (NMDA) receptor hypofunction may cause susceptibility to these behaviours and indicated the importance of environmental conditions in the development of schizophrenia and probably other neuropsychiatric disorders.

Anti-edema effect of Aloe vera leaf extract following traumatic brain injury: Role of pro-inflammatory cytokines.

OBJECTIVE: Based on anti-inflammatory effects of Aloe vera, the effect of aqueous extract of this plant on brain edema and changes in some pro-inflammatory cytokines was investigated after traumatic brain injury (TBI). MATERIALS AND METHODS: In this study, adult male Wistar rats were divided into 5 groups: Sham, TBI, vehicle (Veh), and low dose (LA) and high dose (HA) Aloe vera. The vehicle and aqueous extract of Aloe vera were injected intraperitoneally 30 min after induction of diffuse TBI by Marmarou's method. Brain edema (brain water content), and transforming growth factor beta (TGF-ß), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6) and IL-1ß levels in serum and brain were measured 24 hr after TBI induction. RESULTS: Increased brain edema by TBI was reduced by both LA and HA (p<0.01 and p<0.05, respectively). IL-6 increased in the brain of TBI group compared to sham, and which was inhibited by both Aloe vera doses compared to Veh (p<0.001). The differences in the IL-6 serum levels among Veh, LA and HA groups were not significant. Increases in serum and brain IL-1ß levels were reduced only in the HA group (p<0.001). Although only in the brain, TNF-α level increased after trauma, but both LA and HA inhibited it in a dose-dependent manner (p<0.01 and p<0.05, respectively) . The amount of TGF-ß in the brain was reduced by both doses of the extract (p<0.001). CONCLUSION: These results indicated that Aloe vera has a neuroprotective effect induced by reducing brain edema. The probable mechanism particularly for HA is decreasing levels of pro-inflammatory cytokines such as TGF-ß, TNF-α, IL-6 and IL-1ß.

Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist.

OBJECTIVES: The contribution of classic progesterone receptors (PR) in interceding the neuroprotective efficacy of progesterone (P4) on the prevention of brain edema and long-time behavioral disturbances was assessed in traumatic brain injury (TBI). MATERIALS AND METHODS: Female Wistar rats were ovariectomized and apportioned into 6 groups: sham, TBI, oil, P4, vehicle, and RU486. P4 or oil was injected following TBI. The antagonist of PR (RU486) or DMSO was administered before TBI. The brain edema and destruction of the blood-brain barrier (BBB) were determined. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and beam walk (BW) task were evaluated previously and at various times post-trauma. Long-time locomotor and cognitive consequences were measured one day before and on days 3, 7, 14, and 21 after the trauma. RESULTS: RU486 eliminated the inhibitory effects of P4 on brain edema and BBB leakage (P<0.05, P<0.001, respectively). RU486 inhibited the decremental effect of P4 on ICP as well as the increasing effect of P4 on CPP (P<0.001) after TBI. Also, RU486 inhibited the effect of P4 on the increase in traversal time and reduction in vestibulomotor score in the BW task (P<0.001). TBI induced motor, cognitive, and anxiety-like disorders, which lasted for 3 weeks after TBI; but, P4 prevented these cognitive and behavioral abnormalities (P<0.05), and RU486 opposed this P4 effect (P<0.001). CONCLUSION: The classic progesterone receptors have neuroprotective effects and prevent long-time behavioral and memory deficiency after brain trauma.