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The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats

  • Neuroscience
  • Published:
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Abstract

This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230–260 g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35 mg/kg, i.p) three times a week for a maximum of 10 weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30 min after the PTZ injection. The administration of Hp (0.6 μg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5 μg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5 μg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6 μg, i.c.v) and ACEA (7.5 μg, i.c.v) and of Hp (0.6 μg, i.c.v) and AM-251 (0.5 μg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp’s intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03 μg) + AM-251 (0.125 μg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) [project number 215S808]. The funding source had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

    Ali Al-Kaleel, Lubna Al-Gailani, Mustafa Ayyildiz, Aydin Him & Erdal Agar

  2. Faculty of Medicine, Cyprus International University, Nicosia, Cyprus

    Ali Al-Kaleel & Lubna Al-Gailani

  3. Department of Physiology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey

    Hatice Aygun

  4. Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayis University, Samsun, Turkey

    Yonca Kabak & Sinem Inal

  5. Department of Physiology, Faculty of Medicine, Bolu Abant İzzet Baysal University, Bolu, Turkey

    Aydin Him

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  1. Ali Al-Kaleel
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Contributions

AA., LA., HA, and AH: Conducted the experiments. YK, SI, and MA: Analyzed the data. EA and AA: Wrote the manuscript. EA: Planned and supervised all experiments.

Corresponding author

Correspondence to Ali Al-Kaleel.

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Competing interests

The authors have no relevant financial or non-financial interests to disclose other than the funding source (The Scientific and Technological Research Council of Turkey (TUBITAK) [project number 215S808]) mentioned in the section above.

Ethics approval

The experimental procedures were conducted following the European Union Directive (2010/63/EU) and the Turkish Legislations Acts of experimental animals. The study protocol was approved by the Local Ethical Committee of Ondokuz Mayis University (2015/55).

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Al-Kaleel, A., Aygun, H., Al-Gailani, L. et al. The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats. Pflugers Arch - Eur J Physiol 475, 719–730 (2023). https://doi.org/10.1007/s00424-023-02814-y

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