Occurrence of yawning and decrease of prolactin levels via stimulation of dopamine D2-receptors after administration of SND 919 in rats

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Abstract
SND 919 ((S)-2-amino-4,5,6,7-tetrahydro-6-propylamino-benzothiazole) is expected to have a potent and selective dopamine D2-receptor agonistic activity. From this information, the present study was performed to investigate effects of SND 919 on yawning behavior and prolactin secretion in rats. Subcutaneous injections of SND 919 (25–500 gm/kg, s. c.) elicited yawning responses. Its dose-response curve was bell-shaped with maximal effects at a dose of 100 μg/kg. Yawning behavior was also evoked by the putative dopamine autoreceptor agonists, talipexole (6-allyl2-amino-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]azepine) (BHT 920) (5–100 μg/kg, s. c.) and (+)-3-PPP ((+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine) (5−15 mg/kg, s. c.). The yawning induced by SND 919 (100 μg/kg, s. c.) as well as talipexole (25 μg/kg, s. c.) was inhibited by pretreatment with dopamine D2-receptor antagonists such as spiperone (0.5 mg/kg, i.p.) and YM-09151-2 (cis-N-(1-benzyl-2methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide) (0.1 mg/kg, i. p.), or the muscarinic receptor antagonist, scopolamine (0.5 mg/kg, i.p.). However, the yawning was not affected by the dopamine D1-receptor antagonist, SCH 23390 (R(+)-8-chloro-2,3,4,5-tetrahydro-3methyl-5-phenyl-1 H-3-benzazepine-7-ol) (0.5 mg/kg, i. p.). Stereotypy such as licking and biting was not observed following the administration of SND 919, talipexole and (+)-3-PPP. Administration of SND 919, talipexole or (+)-3-PPP in respective yawn-inducing doses caused a reduction in both the basal prolactin levels and the a-methyl-p-tyrosine-induced hyperprolactinemia. The results suggest that SND 919 as well as talipexole exerts selective agonistic activities for specific dopamine D2-receptors, which are not related to the occurrence of stereotypy and have a high affinity for dopamine receptor agonists quite similar to that of the pituitary lactotroph dopamine D2-receptors.