Behavioral Deficits In Mice Research Articles

Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E

Apolipoprotein E (apoE) is involved in the risk to develop sporadic Alzheimer's disease (AD). Since impaired central acetylcholine (ACh) function is a hallmark of AD, apoE may influence ACh function by modulating muscarinic ACh receptors (mAChRs). To test this hypothesis, mAChR binding was measured in mice lacking apoE and wild type C57BL/6J mice. Mice were also tested on the pre-pulse inhibition, delay eyeblink classical conditioning, and 5-choice serial reaction time tasks (5-SRTT), which are all modulated by ACh transmission. Mice were also given scopolamine to challenge central mAChR function. Compared to wild type mice, mice lacking apoE had reduced number of cortical and hippocampal mAChRs. Scopolamine had a small effect on delay eyeblink classical conditioning in wild type mice but a large effect in mice lacking apoE. Mice lacking apoE were also unable to acquire performance on the 5-SRTT. These results support a role for apoE in ACh function and suggest that modulation of cortical and hippocampal mAChRs might contribute to genotype differences in scopolamine sensitivity and task acquisition. Impaired apoE functioning may result in cholinergic deficits that contribute to the cognitive impairments seen in AD.

Amniotic fluid derived stem cells ameliorate focal cerebral ischaemia-reperfusion injury induced behavioural deficits in mice

The present study has been designed to investigate the effect of amniotic fluid derived stem cells on focal cerebral ischaemia-reperfusion injury induced behavioural deficits in mice. Middle cerebral artery occlusion of 60 min followed by reperfusion for 7 days was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Assessment of cognitive behaviour was done using elevated plus maze. Assessment of neurological severity score was employed to assess motor, sensory, reflex, and balance tests in a composite manner. Adhesive-removal somatosensory test was employed to evaluate somatosensory deficit. Partial occlusion of middle cerebral artery markedly impaired memory, motor coordination, sensorimotor ability and somatosensory functions as inferred from the results of elevated plus-maze test, adhesive-removal test and neurological severity score test. Intracerebroventricular administration of amniotic fluid derived stem cells/embryonic neuronal stem cells significantly reversed the focal cerebral ischaemia-reperfusion induced behavioural deficit measured in terms of loss of short-term memory, motor coordination, sensorimotor ability and somatosensory functions. Therefore, it may be concluded that stem cells derived from amniotic fluid exert beneficial effect on the ischaemic brain to an extent comparable to the neuroprotective effect of embryonic neuronal stem cells.

Long-term evaluation of sensorimotor and mnesic behaviour following striatal NMDA-induced unilateral excitotoxic lesion in the mouse

Excitotoxic lesion of the striatum provides a useful model for evaluating the excitotoxic processes involved in neurological disorders, in particular stroke diseases. The behavioural outcome after such injury is however poorly described. We have therefore investigated the potential behavioural deficits induced by a NMDA-induced excitotoxic unilateral lesion of the lateral part of the striatum, by comparison with a PBS striatal injection (sham procedure), and non-operated mice behaviour. Three groups of male adult Swiss mice were constituted: unilateral NMDA (20 nmol striatal NMDA injection), sham (striatal PBS injection), and control (healthy non-operated mice). From 14 to 29 days post-surgery, sensorimotor and mnesic tests were performed in all groups. After euthanasia, immunohistochemical stainings (NeuN and GFAP) were performed in order to assess the size of the lesion. Straight runway and passive avoidance performances revealed mild deficits related to the excitotoxic NMDA-induced lesion as compared to the sham procedure. Moreover, accelerated rotarod and Morris water maze acquisition performances also revealed deficits related to the surgery, i.e. observed in sham-operated as compared to control mice. NeuN staining revealed no striatal lesion in the sham and non-operated groups in contrast to the NMDA-injected group in which the volume of infarcted striatum was 2.4 ± 0.3 mm 3. GFAP staining revealed a glial reaction in the lesioned striatum of NMDA animals and at the PBS injection site in sham animals. These results suggest that NMDA-induced excitotoxic lesion induces subtle long-term behavioural deficits in mice. Moreover, this study shows the importance of the sham group to investigate the behavioural deficits after excitotoxic lesion models in mice.

Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression

Two receptors for vasopressin (Avp) are expressed in the brain, the Avp 1a receptor (Avpr1a) and the Avp 1b receptor (Avpr1b). To investigate the role of Avpr1a in behaviors in mice more extensively, we generated a line of mice lacking a functional Avpr1a (knockout, Avpr1a(-/-)). We first performed a baseline phenotypic screen of the Avpr1a knockouts followed by a more detailed analysis of their circadian rhythms and olfactory function. When free-running in constant darkness, the Avpr1a(-/-) mice have a longer circadian tau than the wild types. There are also subtle olfactory deficits in Avpr1a(-/-) mice as measured in an olfactory habituation/dishabituation test and in the discrimination of female urine from male urine using an operant testing paradigm. An extensive body of research has shown that manipulation of the Avpr1a alters behavior, including aggression and social recognition. Therefore, we expected profound behavioral deficits in mice lacking the Avpr1a gene. Contrary to our expectations, social aggression, anxiety-like behavior and social recognition are unaffected in this line of Avpr1a knockout mice. These data suggest either that the Avpr1a is not as critical as we thought for social behavior in mice or, more likely, that the neural circuitry underlying aggression and other social behaviors compensates for the life-long loss of the Avpr1a. However, the olfactory deficits observed in the Avpr1a(-/-) mice suggest that Avp and Avpr1a drugs may affect behavior, in part, by modulation of chemosensory systems.

Grid performance test to measure behavioral impairment in the MPTP-treated-mouse model of parkinsonism

Behavioral impairments in mice following administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) require large depletions in striatal dopamine content and are often transient. In this paper, we describe a simple and inexpensive test that measures long-term behavioral deficits in mice treated with moderate doses of MPTP. These measures are significantly correlated with the loss of striatal dopamine and immunoreactivity of the dopamine transporter, vesicular monoamine transporter and tyrosine hydroxylase. In addition, behavioral impairments on the measures were reversed following l-DOPA administration. Employment of this test will allow for more efficacious use of mice in PD research, as well as provide more sensitive measures of behavioral improvement following potential therapeutic or neuroprotective interventions.

Effects of nortriptyline treatment on learned helplessness in the rat

Using an escape delay procedure previously shown to elicit behavioral deficits in mice exposed to uncontrollable shock, rats treated with inescapable shock or no shock displayed comparable interference effects when tested in a two-way shuttle box 24 hr later. Treatment with 12.5 mg/kg nortriptyline for 4 or 6 days counteracted the escape deficits by produced by inescapable shock while the 0 or 2 day administration regimens were without any appreciable effect. The finding that interference effects produced by inescapable shock were sensitive to sub-acute but not acute drug adminitration supports the utility of the learned helplessness model in evaluating potential antidepressant agents in experimental animals.