We examined the effects of neonatal treatment with MK-801 on 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shaking as well as [(3)H]ketanserin binding in adult rats. Neonatal rats were injected with MK-801 (0.25 mg/kg, s.c., twice daily) or with saline from postnatal days (PND) 7-18. At PND 60, a statistically significant increase in the frequency of head shaking induced by DOI (1.0 mg/kg, s.c.) was observed in the rats neonatally treated with MK-801, compared to saline-treated rats, without any change in the specific [(3)H]ketanserin binding in the frontal cortex. These results suggest that repeated NMDA receptor blockades during the critical period of brain development produce a long lasting hyper-responsiveness in the 5-HT(2A) receptor-mediated behavior, interfering with the development of neural circuits related to the behavior.
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Assessing the effects of 5-HT and 5-HT receptor antagonists on DOI-induced head-twitch response in male rats using marker-less deep learning algorithms.
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Serotonin 2A receptors (5-HT Rs) mediate the effects of psychedelic drugs. 5-HT R agonists, such as (-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), that produce a psychedelic experience in humans induce a head-twitch response (HTR) behavior in rodents. However, it is unknown whether the activity of 5-HT R expressing neurons is sufficient to produce the HTR in the absence of an agonist, or in which brain region 5-HT Rs control the HTR.
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