| Abstract No.: | C-C3107 |
| Country: | Canada |
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| Title: | THE IMPACT OF NEONATAL THALAMIC LESION ON THE DOPAMINERGIC MODULATION OF LOCOMOTOR ACTIVITY IN PREPUBERTAL RATS |
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| Authors/Affiliations: | 1 Ian Mahar*; 1 Bonnie Clarke; 1 Yukiori Goto;
1 McGill University, Montreal, QC, Canada
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| Content: | Objectives: The prefrontal cortex (PFC) receives excitatory input from various cortical and subcortical structures, including the thalamus. Accumulating evidence suggests that thalamic input regulates dopamine (DA) receptor expression in the cortex during early brain development. In this study, we examined the impact of neonatal thalamic lesions on locomotor activity in prepubertal rats in response to the DA agonist apomorphine (APO).
Materials and Methods: Bilateral thalamic lesions (THAL; n=5) were performed on male pups at postnatal day 7-8 using ibotenic acid. Control animals (SHAM; n=12) received phosphate-buffered saline (PBS). At postnatal day 28-35, each animal was placed in a locomotor chamber (.4mX.4mX.35m) and its activity was recorded for 20 minutes. Five minutes prior to testing, APO (.75mg/kg) or PBS was administered i.p. Lesions were confirmed histologically following testing.
Results: Spontaneous locomotion (following saline injection) was slightly higher for THAL rats (22.5 ± 2.6 m; mean ± S.D.) than that of SHAM animals (19.7 ± 8.1 m). When apomorphine was administered, locomotor activity in THAL rats was decreased (17.7 ± 12.1 m), whereas activity in SHAM rats was increased (30.1± 23.6 m).
Conclusion: We found that spontaneous locomotion was higher for THAL than SHAM rats. Moreover, administration of APO decreased locomotor activity in THAL rats, but increased activity in SHAM rats. These results suggest that neonatal thalamic lesions produce alterations of the DA system in prepubertal animals by which spontaneous locomotor activity is increased, and response to DA agonists is reversed in comparison to SHAM rats. Such increased spontaneous hyperactivity and its reduction by a DA agonist appears to be consistent with attention deficit/hyperactivity disorders.
ACKNOWLEDGMENTS: This study was supported by McGill University Health Center, and the CIHR.
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