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Ritanserin blocks DOI-altered embryonic motility and posthatch learning in the developing chicken
Abstract:
Developing chicken embryos exposed to cocaine show altered motility, hatchability, and posthatch detour learning. Pretreating such subjects with the serotonin2 (5-HT2) antagonist ritanserin (RIT) can block the motility suppression and reduced hatchability, indicating 5-HT2 receptor involvement in these cocaine effects. To study behavioral consequences of more selective 5-HT2 receptor stimulation and its blockade during development and to compare such exposure with that of cocaine, we injected eggs with 15-day-old chicken embryos with the 5-HT2 agonist dimethoxyiodophenylaminopropane (DOI, 1.0 mg/kg egg) and 1 h later, with RIT (0.3 and 0.9 mg/kg egg). Motility was recorded 2.5 or 24 h after DOI. This DOI dose suppressed motility 2.5 h but not 24 h after administration. Both RIT doses blocked DOI's motility suppression. No treatment affected hatchability. Subjects were tested on posthatch days 6-9 for detour learning acquisition. DOI "enhanced" learning (i.e., reduced latency), a cocaine-like effect observed in prior work, which was also blocked by both RIT doses. Thus, some consequences of DOI exposure late during embryonic development resemble cocaine's and are blocked by RIT, suggesting a therapeutic role for RIT-like drugs against cocaine's potential developmental toxicity.
Insights
Cocaine exposure during embryonic development affects chicken embryo behavior. The drug ritanserin (RIT) blocks some of these effects, suggesting RIT-like drugs may counteract cocaine's developmental toxicity.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Cocaine exposure in developing chicken embryos alters motility, hatchability, and learning.
- Serotonin 2 (5-HT2) receptor antagonism with ritanserin (RIT) mitigates some cocaine-induced effects, suggesting 5-HT2 receptor involvement.
Purpose of the Study:
- To investigate the behavioral effects of selective 5-HT2 receptor stimulation and blockade during embryonic development.
- To compare the developmental effects of a 5-HT2 agonist with those of cocaine.
Main Methods:
- Chicken embryos at 15 days of development were injected with the 5-HT2 agonist dimethoxyiodophenylaminopropane (DOI).
- Ritanserin (RIT) was administered 1 hour after DOI to assess blockade effects.
- Motility was recorded at 2.5 and 24 hours post-DOI; hatchability was monitored.
- Posthatch detour learning was assessed in treated subjects.
Main Results:
- DOI (1.0 mg/kg) transiently suppressed motility at 2.5 hours, an effect blocked by both RIT doses (0.3 and 0.9 mg/kg).
- No significant effects on hatchability were observed with any treatment.
- DOI exposure enhanced detour learning acquisition (reduced latency), a cocaine-like effect, which was also blocked by RIT.
Conclusions:
- Selective 5-HT2 receptor stimulation with DOI during late embryonic development produces some cocaine-like behavioral effects.
- Ritanserin effectively blocks these DOI-induced behavioral changes, including altered motility and enhanced learning.
- These findings suggest a potential therapeutic role for ritanserin-like drugs in mitigating cocaine's developmental toxicity.