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The 6‐hydroxydopamine unilaterally‐lesioned rat as an in vivo model for novel dopaminergic compounds and antipsychotic drugs
Author(s) -
Boyd Kevin N,
Murthy Vishakantha,
Mailman Richard B.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1045.1
Subject(s) - quinpirole , dopaminergic , pharmacology , dopamine , dopamine receptor , neuroscience , hydroxydopamine , apomorphine , in vivo , medicine , antipsychotic , oxidopamine , biology , schizophrenia (object oriented programming) , substantia nigra , microbiology and biotechnology , psychiatry
Modulation of dopamine systems is an important therapeutic strategy, but desired effects and side effects are often elicited simultaneously. Recent advances (e.g., allosteric or functionally selective drugs) provide a route to superior drugs, but translating in vitro data to the intact animal is difficult. We investigated whether the 6‐OHDA unilateral‐lesioned rat model could differentiate functionally selective dopamine ligands and antipsychotic drugs (APDs). Male Sprague‐Dawley rats were lesioned (MFB) and verified by apomorphine‐induced contralateral rotations. Typical and atypical APDs and functionally selective ligands were tested alone and versus quinpirole. Quinpirole‐mediated rotations were inhibited by typical and most atypical APDs, but not by functionally selective ligands. Importantly, no clinically approved APD caused rotations on its own, but several APD compounds that failed clinical trials caused rotations on their own and did not block quinpirole. Although widely considered a model of Parkinson's disease, these data suggest that this model may be a useful addition for screening novel APDs. The pattern of action on dopamine signaling pathways highlights some of the critical signaling pathways and may help translate novel drugs to the clinic.