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Chronic neonatal treatment with CGS 8216: effects on the behaviour of adolescent rats
Insights
Neonatal exposure to CGS 8216 altered adolescent rat behavior, reducing sensitivity to convulsants but not affecting social interaction responses. These findings differ from adult responses to CGS 8216.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- Neonatal drug administration can lead to long-term behavioral changes.
- CGS 8216 is a benzodiazepine receptor antagonist with known effects on adult behavior.
Purpose of the Study:
- To investigate the lasting behavioral effects of neonatal CGS 8216 administration in male adolescent rats.
- To compare adolescent responses to CGS 8216 with known adult responses.
Main Methods:
- Male rat pups received daily CGS 8216 (2.5 or 10 mg/kg/day) from postnatal day 7 to 28.
- Cross-fostering was employed, and behavioral tests commenced on day 31.
- Tests included social interaction, holeboard exploration, and responses to convulsant agents (pentylenetetrazole, picrotoxin).
Main Results:
- Neonatal CGS 8216 induced an unusual social interaction profile in adolescents, opposite to adult acute effects.
- Adolescents showed reduced sensitivity to the convulsant effects of pentylenetetrazole and picrotoxin.
- Exploratory behavior and responses to Ro 15-1788 or chlordiazepoxide were largely unaffected.
Conclusions:
- Neonatal CGS 8216 administration induces lasting behavioral alterations in adolescent rats.
- These adolescent effects are not identical to those observed in adult rats, particularly regarding proconvulsant effects.
Abstract:
The behaviour of male adolescent rats was studied after neonatal administration of CGS 8216 (2.5 or 10 mg/kg/day). The pups were cross-fostered, and drug treatment (in a split-litter design) lasted from postnatal day 7 to day 28; behavioural tests began on day 31. In the social interaction test, neonatally-treated adolescents displayed an unusual profile of behaviour that was the opposite to the profile caused by acute CGS 8216 in adults. Their response to challenge doses of CGS 8216 was not significantly different from that of neonatal controls. In the holeboard test of exploratory behaviour, there was little sign of effects of the neonatal treatment, and the response to challenge doses of Ro 15-1788 or chlordiazepoxide was not differentially affected. However, neonatally-treated animals were less sensitive to the convulsant effects of pentylenetetrazole and picrotoxin. Lasting effects of neonatal CGS 8216 have been detected in adults; the effects seen in adolescents appear not to be identical, since a proconvulsant effect occurs in adults.