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Effects of morphine and methadone treatments on glutamatergic transmission in rat frontal cortex
Bartosz Bobula1, Grzegorz Hess
1Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Abstract:
The effects of repeated administration of morphine and methadone, followed by a challenge dose of either morphine or methadone were examined ex vivo in rat frontal cortical slices that were prepared 1 h after final drug administration. Morphine challenge dose (5 mg/kg), administered 14 days after the end of repeated morphine pretreatment (10 mg/kg, administered 7 times) decreased both the AMPA/kainate and the NMDA components of field potentials that were evoked in cortical layer II/III by electrical stimulation. This effect did not occur either when a methadone challenge dose (2.5 mg/kg) was administered instead of morphine or after repeated morphine treatment. Moreover, after repeated methadone treatment (2.5 mg/kg, administered 7 times), neither morphine nor methadone challenge affected AMPA/kainate or NMDA components of the field potentials. These data indicate a specific effect of repeated morphine followed by morphine challenge on cortical glutamatergic transmission.
Insights
Repeated morphine, but not methadone, pretreatment specifically reduced cortical glutamatergic transmission. A subsequent morphine challenge dose further decreased AMPA/kainate and NMDA receptor activity in rat brain slices.
Area of Science:
- Neuroscience
- Pharmacology
- Neurochemistry
Background:
- Opioid analgesics like morphine and methadone are widely used.
- Understanding their long-term effects on brain function is crucial.
- Glutamatergic neurotransmission plays a key role in brain activity.
Purpose of the Study:
- To investigate the specific effects of repeated morphine or methadone administration on cortical glutamatergic transmission.
- To examine the impact of challenge doses of these opioids after repeated pretreatment.
Main Methods:
- Ex vivo electrophysiological recordings from rat frontal cortical slices.
- Repeated administration of morphine (10 mg/kg) or methadone (2.5 mg/kg) for seven days.
- Challenge doses of morphine (5 mg/kg) or methadone (2.5 mg/kg) administered after a 14-day washout period.
Main Results:
- Repeated morphine pretreatment followed by a morphine challenge significantly decreased both AMPA/kainate and NMDA components of evoked field potentials.
- This specific effect was not observed when a methadone challenge was used after morphine pretreatment.
- Neither morphine nor methadone challenge doses affected these glutamatergic components after repeated methadone pretreatment.
Conclusions:
- Repeated morphine administration followed by a morphine challenge specifically alters cortical glutamatergic transmission.
- Methadone does not produce the same specific alterations in cortical glutamatergic transmission.
- These findings highlight differential neurochemical effects of chronic morphine and methadone exposure.
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