Effects of intrastriatal infusion of D2 receptor antisense oligonucleotide on apomorphine-induced behaviors in the rat

✍ Scribed by N. Rajakumar; L. Laurier; H.B. Niznik; A.J. Stoessl

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 306 KB
• Volume: 26
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199707)26:3<199::aid-syn1>3.0.co;2-2

✦ Synopsis

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.