Impaired Spatial Learning and Reduced MK-801 Associated Behavioral Deficits in Rodents Following Early Postnatal Exposure to

نویسنده

  • Jing Guo
چکیده

The current research aimed to investigate the effects of early postnatal exposure to low-level lead on the spatial learning of Long-Evans Hooded rats tested in the Morris water maze. To explore possible neurotoxic actions of lead on the N-methyl-D-aspartate (NMDA) receptors, the noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydroxy-5hdibenzo(a,d)cyclohepten-5,10-imine (MK-801) was used. Two-day-old pups were randomly assigned to 0.1% lead carbonate diet or control diet and weaned onto regular food on postnatal day (PND) 23. Spatial acquisition was assessed from PND 24 to PND 27. Thirty minutes prior to behavioral testing, rats received an intraperitoneal (i.p.) injection of 0.1% MK-801 or saline. In the saline treatment group, Pb-exposed rats exhibited significantly longer overall mean escape latencies than those on the control diet, replicating the impaired spatial learning of Pb-exposed animals tested at a young age. Although MK-801 injection severely impaired animals’ water maze performance regardless of diet, it affected the performance of Pb-exposed animals to a lesser extent than animals on the control diet. No main effects of diet and drug were found for probe trials on PND 28 and PND 36, but interestingly, lead diet/MK-801 animals performed significantly better than control diet/MK-801 animals during the first probe trial. Unfortunately, MK-801 not only caused animals to display higher activity levels in the activity box, but also significantly impaired animals’ performance in the cued trial, suggesting non-specific sensorimotor deficits induced by MK-801 treatment might be responsible for animals’ poor performance. However, a significant drug by diet interaction in the escape latencies and the significantly better probe trial performance of Pb-exposed animals within the MK-801 treatment group imply that lead exposure actually alleviated behavioral deficits induced by MK-801 injection, providing evidence for a possible interaction between lead and MK-801 at the molecular level.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Chronic neonatal N-methyl-D-aspartate receptor blockade induces learning deficits and transient hypoactivity in young rats.

A blockade of N-methyl-D-aspartate (NMDA)-type of glutamate receptor in rodents is believed to provide a pharmacological model of schizophrenia-related psychosis. Since neurodevelopmental abnormality, at least partly, could contribute to the pathogenesis of schizophrenia, the aim of this study was to recapitulate cognitive impairments accompanying this disorder in rats by a chronic neonatal tre...

متن کامل

Spatial discrimination reversal learning in weanling rats is impaired by striatal administration of an NMDA-receptor antagonist.

The striatum plays a major role in both motor control and learning and memory, including executive function and "behavioral flexibility." Lesion, temporary inactivation, and infusion of an N-methyl-d-aspartate (NMDA)-receptor antagonist into the dorsomedial striatum (dmSTR) impair reversal learning in adult rats. Systemic administration of MK-801 disrupts reversal learning in developing rats, a...

متن کامل

Effect of ecstasy microinjection on spatial memory and it’s interaction with glutamatergic system in male rats

Introduction: Ecstasy is an amphetamine derivative, which its use has been consistently increasing over the past years. Ecstasy interacts with the glutamatergic system and it is known that glutamate receptors have a key role in learning and memory. The aim of this study was to investigate the interaction of ecstasy and glutamatergic system on learning and memory. Methods: Fifty-six male Wis...

متن کامل

Selective Activation of M4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents

Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that e...

متن کامل

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence.

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task tha...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2007