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The effects of nicotine and methylphenidate on abnormal behaviors in reelin deficient mice: potential animal models for neurodevelopmental disorders.

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Pamela Ladrow, Lecturer (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Walter Salinger

Abstract: Behavioral abnormalities exhibited by reelin deficient mice may model behavioral deficit characteristics that are associated with schizophrenia, bipolar disorder, autism, and/or attention deficit hyperactivity disorder (ADHD). To expand upon the behavioral phenotype of reelin deficient mice, the effects of methylphenidate (MPH) and nicotine (NIC) were evaluated on specific behaviors in homozygous (rl/rl, 100% deficient), heterozygous (+/rl, 50% deficient), and wild-type (+/+, 0% deficient) mice to determine if drugs would differentially influence behavior depending on level of reelin deficiency, and to determine if responses to drug treatments modeled effects that would be predicted, assuming mice modeled impairments associated with schizophrenia, bipolar disorder, autism, or ADHD. In addition, NIC and saccharin vehicle (S-VEH) intake levels were measured to determine if mice self-administer NIC differently depending on genotype. A non-linear gene dosage effect of NIC, but not MPH, was observed in prepulse inhibition (PPI), such that NIC improved PPI in +/+ and rl/rl mice, while NIC tended to reduce abnormally elevated startle response and PPI in +/rl mice. During NIC self-administration trials, +/rl mice decreased NIC intake when concentration of NIC increased to 60 mg/kg/BW, while rl/rl mice tended to increase NIC intake with increased NIC concentration. Moreover, +/rl and rl/rl mice exhibited elevated levels of S-VEH intake, and rl/rl mice exhibited an intensified fluid dispenser side bias compared to +/+ mice. In tests of social interaction, rl/rl mice displayed impaired social recognition. In addition, NIC +/rl mice exhibited increased social behavior, while NIC rl/rl mice displayed decreased social behavior. In the passive avoidance (PA) test, all genotypes demonstrated the ability to withhold a response--which is a measure executive functioning--and rl/rl mice demonstrated enhanced performance. In addition, MPH produced enhanced performance in +/rl mice and rl/rl compared to VEH condition. Thus, behavioral outcomes and pharmacological responses in the present study expand upon profiles of +/rl and rl/rl mice, offer guidance about which behaviors across and/or within diagnostic categories may be most profitably modeled by behavioral features of these mice, and may provide insight into underlying neurobiological pathology associated with altered cholinergic and dopaminergic pathways as a consequence of disrupted reelin production.

Additional Information

Publication
Dissertation
Language: English
Date: 2009
Keywords
Autism, Methylphenidate, Neurodevelopmental, Nicotine, Reelin, Schizophrenia
Subjects
Brain $x Diseases $x Pathogenesis.
Cognition disorders $x Research.
Affective disorders $x Research.
Nicotine.
Methylphenidate.