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Stimulatory and inhibitory effects of morphine on pentylenetetrazol-induced epileptic activity in rat
Samrand Rashan1, Yousef Panahi2, Emad Khalilzadeh3
1Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Aims:
The present study attempts to evaluate the effects of different doses of morphine on experimental epileptiform activity caused by pentylenetetrazol (PTZ) in rats.
Methods:
Thirty adult male rats were assigned to saline (n = 5), morphine (2, 5, and 10 mg/kg, n = 15), naloxone (1 mg/kg, n = 5), and pre-treated with naloxone+morphine (1 + 10 mg/kg, n = 5) groups. The animals were anesthetized with ketamine + xylazine (80 + 8 mg/kg), and then a bipolar electrode was implanted into the CA1 (AP: -2.76 mm, ML: -1.4 mm and DV: 3 mm). To evaluate the effects of drugs on spike count and their amplitudes by elab amplifier, after drug administration for 25 min, PTZ (80 mg/kg, i.p.) was injected to induce epileptiform activity. Finally, diazepam (10 mg/kg) was used to suppress epileptic activity.
Results:
The results revealed that morphine at a dose of 2 mg/kg decreased, and at doses of 5 and 10 mg/kg had an increasing effect on seizure-like events (SLEs). Nevertheless, morphine at a dose of 10 mg/kg enhanced SLEs significantly (p < 0.01). Naloxone at a dose of 1 mg/kg had no significant effect on the spike count but increased amplitude of them (p < 0.001). Moreover, being pretreatment with naloxone at a dose of 1 mg/kg, the morphine group showed significantly increased in the spike count (p < 0.05).
Conclusions:
Morphine has biphasic effects on PTZ-induced epileptiform activities that way at a low dose has an inhibitory effect, but if the dose is increased, it will intensify the desired event and that the stimulatory effects of morphine appear not to be via opioid receptors.
Insights
Morphine exhibits biphasic effects on pentylenetetrazol (PTZ)-induced seizures in rats. Low doses inhibit, while higher doses exacerbate epileptiform activity, suggesting non-opioid receptor involvement.
Area of Science:
- Neuroscience
- Pharmacology
- Epilepsy Research
Background:
- Epileptiform activity can be experimentally induced using pentylenetetrazol (PTZ).
- The effects of opioids, such as morphine, on seizure activity are complex and may be dose-dependent.
- Understanding these effects is crucial for managing seizure disorders and opioid-related side effects.
Purpose of the Study:
- To investigate the dose-dependent effects of morphine on PTZ-induced epileptiform activity in a rat model.
- To explore the potential involvement of opioid receptors in morphine's effects on seizures.
Main Methods:
- Adult male rats were administered varying doses of morphine (2, 5, 10 mg/kg), naloxone, or saline.
- Epileptiform activity was induced by intraperitoneal injection of PTZ (80 mg/kg) after drug administration.
- Electrophysiological recordings were performed in the CA1 region of the hippocampus to measure spike count and amplitude.
Main Results:
- Morphine at 2 mg/kg decreased seizure-like events (SLEs), while 5 and 10 mg/kg increased SLEs.
- A significant enhancement of SLEs was observed with morphine at 10 mg/kg (p < 0.01).
- Naloxone (1 mg/kg) alone did not affect spike count but increased amplitude (p < 0.001); however, naloxone pretreatment enhanced morphine's effect on spike count (p < 0.05).
Conclusions:
- Morphine demonstrates biphasic effects on PTZ-induced epileptiform activity, acting as an inhibitor at low doses and a potentiator at higher doses.
- The stimulatory effects of morphine on epileptiform activity appear to be mediated through non-opioid receptors.
- These findings highlight the complex interaction between morphine and seizure mechanisms.
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