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Effects of intrastriatal infusion of D 2 receptor antisense oligonucleotide on apomorphine‐induced behaviors in the rat
Author(s) -
Rajakumar N.,
Laurier L.,
Niznik H.B.,
Stoessl A.J.
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199707)26:3<199::aid-syn1>3.0.co;2-2
Subject(s) - apomorphine , dopamine receptor d2 , neuroscience , receptor , pharmacology , chemistry , psychology , medicine , agonist , biochemistry
An antisense oligonucleotide strategy was employed to specifically deplete postsynaptic striatal D 2 receptors in order to determine the possible role of presynaptic D 2 autoreceptors in mediating behavioral responses induced by low doses of apomorphine. A phosphorothioate‐modified antisense oligonucleotide complementary to the first 19 bases of the coding region of D 2 receptor mRNA, a scrambled sequence comprising the same bases, or saline was infused bilaterally into the striatum of adult rats, twice daily for 2 days via indwelling cannulae. After an interval of 8–12 h, rats were habituated and challenged with high (300 μg/kg; subcutaneous) or low (50 μg/kg; s.c.) doses of apomorphine or its vehicle (0.1% ascorbic acid). Yawning, vacuous chewing mouth movements, hypoexploration, and penile grooming induced by low‐dose apomorphine were unaffected by antisense infusion into the striatum, whereas stereotypic sniffing following high‐dose apomorphine was markedly suppressed. Intrastriatal infusion of antisense resulted in significantly diminished [ 3 H]‐raclopride binding, while binding of [ 3 H]‐SCH 23390 (D 1 receptors) and [ 3 H]‐WIN 35428 (dopamine transporter) was unchanged. D 2 mRNA levels determined by quantitative in situ hybridization were normal in the striatum and the substantia nigra. Our results confirm that stereotypic sniffing is mediated via postsynaptic D 2 receptors in the striatum, and favor the notion that behavioral responses induced by low doses of apomorphine are mediated by presynaptic D 2 autoreceptors. Synapse 26:199–208, 1997. © 1997 Wiley‐Liss Inc.