Exposure to varenicline protects against locomotor alteration in a MPTP mouse model of Parkinson's disease.

The beneficial effects of drugs that act via nicotinic acetylcholine receptors (nAChRs) on Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition. Varenicline, an α4ß2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated varenicline effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to varenicline (2 mg/kg) by gavage. After that, MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate dopamine and DOPAC levels. To verify whether varenicline was protective during the MPTP insult, a separate group of MPTP animals received varenicline from PN90 to PN124. MPTP reduced cortical dopamine content and increased dopamine turnover. Those effects were not reversed by varenicline treatment. Interestingly, varenicline reversed the MPTP-induced hyperactivity in the open field. Both maintenance of varenicline treatment during MPTP exposure or its interruption before MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that varenicline treatment reduced the MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect, varenicline could exert neuroprotective effects on circuits that control motor activity in PD.

Exposure to varenicline protects against locomotor alteration in a MPTP mouse model of Parkinson's disease

The beneficial effects of drugs that act via nicotinic acetylcholine receptors (nAChRs) on Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition. Varenicline, an α4β2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated varenicline effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to varenicline (2 mg/kg) by gavage. After that, MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate dopamine and DOPAC levels. To verify whether varenicline was protective during the MPTP insult, a separate group of MPTP animals received varenicline from PN90 to PN124. MPTP reduced cortical dopamine content and increased dopamine turnover. Those effects were not reversed by varenicline treatment. Interestingly, varenicline reversed the MPTP-induced hyperactivity in the open field. Both maintenance of varenicline treatment during MPTP exposure or its interruption before MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that varenicline treatment reduced the MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect, varenicline could exert neuroprotective effects on circuits that control motor activity in PD.

Combined Application of Entomopathogenic Nematodes and Insecticides in the Control of Leaf-Miner Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) on Tomato.

The present research aimed to investigate the compatibility of entomopathogenic nematodes (EPNs) and registered insecticides for the control of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) in the tomato crop, as well as the susceptibility of pupae of T. absoluta to EPNs combined with different percentages below the recommended dose of compatible chemical insecticides in laboratory conditions and in the greenhouse. The species of EPN used was Heterorhabditis amazonensis JPM4. The insecticides used were Actara®, Premio®, and Warrant®. In the compatibility test between the EPNs and insecticides, the viability and infectivity of the nematodes after contact with the insecticides were evaluated. An assessment of the efficacy of the combined application of different doses of the insecticides and the EPNs on T. absoluta was carried out in the laboratory and greenhouse. The efficacy of the combined application of the insecticides and the EPNs on T. absoluta via soil was carried out at application intervals of 1 and 2 weeks. The EPNs were compatible with the three insecticides tested. In the laboratory, there was an additive effect of the combined application of insecticides and H. amazonensis as the dose of the products increased. In the greenhouse assay, the combined application of EPNs and insecticides induced mortality above 48%, and the combined application of EPNs and Warrant® 75% presented 60% of mortality. The weekly and fortnightly applications were effective in controlling T. absoluta, and there was no difference between the insecticides tested when applied together with the nematodes.

Hippocampal increased cell death and decreased cell density elicited by nicotine and/or ethanol during adolescence are reversed during drug withdrawal.

We have recently identified hippocampal cell death and reduced neuronal and glial cells densities during adolescent nicotine and ethanol exposures and outcomes reduced in severity when nicotine and ethanol are co-administered during this developmental period. In the present study, we investigated the effects of adolescent nicotine and/or ethanol withdrawal on the following regions of the hippocampus: Granular layer of the Dentate Gyrus (GrDG), Molecular layer (Mol), CA1, CA2 and CA3. From the 30th to the 45th postnatal day (PN30-PN45), C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50 microg/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We evaluated cell degeneration (TUNEL assay), neuronal and glial densities (optical Disector) and region thicknesses two (PN47) and five (PN50) days post-exposure. On PN47, there were increases in the number of TUNEL+ cells in most hippocampal regions of both ETOH and NIC groups. In the NIC+ETOH group there were less severe effects. These results were paralleled by reductions in neuronal and glial cells densities for all treatment groups. In contrast, on PN50, ethanol and/or nicotine withdrawal were associated with compensatory reductions in TUNEL+ cells in all hippocampal regions. These results were paralleled by a reversal of effects on neuronal and glial densities so that there were no longer differences between groups. There were no effects on region thicknesses. These results suggest that deleterious effects of nicotine and/or ethanol are reversed during prolonged withdrawal.

Combined exposure to nicotine and ethanol in adolescent mice: effects on the central cholinergic systems during short and long term withdrawal.

Relapse to drug use is a major public health problem. In this sense, understanding the biological substrates that are affected during withdrawal may provide information to prevent relapse. Both smoking and alcoholic beverage consumption usually begin during adolescence, however, little is known about the basic neurobiology of the combined adolescent exposure, particularly during withdrawal. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChRs), the current study focused on the effects of drug withdrawal on the central cholinergic system. From the 30th to the 45th postnatal day (PN), C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50 microg/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We assessed nAChR binding, choline acetyltransferase (ChAT) activity and [(3)H]hemicholinium-3 (HC-3) binding in the cerebral cortex and midbrain of mice at short (PN50) and long term (PN75) withdrawal. NIC and NIC+ETOH promoted nAChR upregulation during a short-term withdrawal. NIC short-term withdrawal elicited an increase in ChAT activity that was reversed by ETOH withdrawal. In addition, NIC+ETOH elicited a decrease in ChAT activity at long term withdrawal. Regarding HC-3, ETOH and NIC+ETOH promoted a decrease that persisted at long-term withdrawal. The present study provides experimental evidence that nicotine and ethanol during adolescence interact resulting in cholinergic system alterations during withdrawal.

Contralateral rotatory bias in the free-swimming test after unilateral hemispherectomy in adult Swiss mice.

In the free-swimming rotatory test mice spend most of the time swimming close to the wall of the container attempting to escape from an aversive test situation. The attraction to the wall may suggest that turning behavior in the free-swimming test reflects the existence of intrinsic sensory asymmetries, which determine preferential attention adhesion to one side. In order to test this hypothesis, we investigated the rotatory swimming behavior of mice submitted to a unilateral hemispherectomy at adulthood, a condition of extreme sensory asymmetry. Fifteen days after surgery procedures, each mouse was tested for 5 min on 3 different days. We found that the hemispherectomized mice had a significant strong bias to turn in the direction contralateral to their lesion. These data could be explained considering that, in attempting to escape from the test situation, animals bring the recipient wall into their intact sensory field and, as a consequence, set the direction of locomotion. Thus, the free-swimming test may be useful to investigate sensory asymmetries during an aversive test situation.

The effects of hand preference and gender on finger tapping performance asymmetry by the use of an infra-red light measurement device.

We used an infra-red device to study the effects of gender and handwriting preference on manual asymmetry in tapping rate and intertap variability. Our sample (n=102) consisted of approximately equal number of subjects with respect to gender (52 women and 50 men) and handedness (52 right-handers and 50 left-handers). Data on overall performance indicated that men performed more quickly and regularly than women. The index used for measuring manual asymmetry was the difference between the hands as a proportion of the total. Therefore, the asymmetry index was adjusted to remove the influence of overall performance. The analyses based on asymmetry scores indicated a significant handedness effect: right-handers showed greater manual asymmetries than left-handers for both tapping rate and intertap variability. In addition, right handers exhibited a significant greater asymmetry for intertap variability than tapping rate. Taken together, these data may reflect greater hemispheric differences in right-handers, specially for intertap variability.

Effects of sex and laterality on the rotatory swimming behavior of normal mice.

Clockwise and counterclockwise full turns are commonly used to assess lateralization in circling behavior. Although previous studies have reported that the rotatory swimming (ROSW) test is simple and reliable, little is known about lateralization of turns lower than 360 degrees and the amount of turning close to the wall, and even less is known about alternation of direction during a session. Here we investigated the effects of consistency of laterality and sex on 30 degree turns in center and in periphery of the swimming apparatus, and on alternation of direction upon three sessions. Approximately 80% of the turns occurred when mice swam along the wall. In side-consistent turners, this suggests the existence of an intrinsic sensorimotor asymmetry that determines the adhesion to the preferred side. Regarding categorization of side preferences, there was a high percentage of agreement between center and periphery, as well as between full turns and extra 30 degree turns (30 degree turns that do not contribute to full turns). Therefore, behavioral asymmetry in the ROSW can be assessed using 30 degree turns. There was no significant directional bias in the population, and side preference was found to be independent of sex. By contrast, after the second minute of each session, males exhibited a significantly higher number of reversal of direction (RD) as well as a higher number of RD per turn than females. The amount of RD presented by each animal is not predicted by the animal's side preference. Thus, RD is independent of preferred side of turning and depends on sex.