Naloxone epileptogenesis in monkeys

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Naloxone is used clinically to reverse opiate effects.
• There are concerns regarding naloxone's potential epileptogenic properties.

Purpose of the Study:

• To investigate the electroencephalographic (EEG) effects of various naloxone doses.
• To understand the dose-dependent neurological impact of naloxone.

Main Methods:

• Recorded electrographic activity from epidural electrodes in eight monkeys.
• Performed visual inspection and power spectral analyses of EEG data.
• Analyzed concurrent visual evoked potentials.

Main Results:

• High-dose naloxone ( > 32.0 mg/kg) reliably induced cortical seizure activity.
• Lower doses ( >= 8.0 mg/kg) increased high-frequency EEG voltage and spiking.
• Visual evoked potential latencies were consistently extended.
• EEG changes were time- and dose-dependent, with early high-dose effects mimicking maximal low-dose effects.

Conclusions:

• Seizures induced by high-dose naloxone (48.0-64.0 mg/kg) stem from changes observable at clinically relevant doses.
• These dose-dependent neurological alterations may not be obvious upon routine visual EEG inspection.