Modulation of the CB1 cannabinoid receptor has potential therapeutic utility in the 3-acetylpyridine cerebellar ataxia rat model
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Modulation of the CB1 cannabinoid receptor has potential therapeutic utility in the 3-acetylpyridine cerebellar ataxia rat model. / Ranjbar, Hoda; Soti, Monavareh; Janahmadi, Mahyar; Kohlmeier, Kristi A; Sheibani, Vahid; Ahmadi-Zeidabadi, Meysam; Shabani, Mohammad.
In: Experimental Brain Research, Vol. 240, 2022, p. 2339–2348.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Modulation of the CB1 cannabinoid receptor has potential therapeutic utility in the 3-acetylpyridine cerebellar ataxia rat model
AU - Ranjbar, Hoda
AU - Soti, Monavareh
AU - Janahmadi, Mahyar
AU - Kohlmeier, Kristi A
AU - Sheibani, Vahid
AU - Ahmadi-Zeidabadi, Meysam
AU - Shabani, Mohammad
N1 - © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022
Y1 - 2022
N2 - Cerebellar ataxia is a neurodegenerative disorder leading to severe motor incoordination. Recently, it has been suggested that cannabinoids play a role in modulating ataxic symptoms. To understand the possible therapeutic effect of cannabinoids for the management of cerebellar ataxia, we used cannabinoid agonist/antagonists to target the cannabinoid type 1 receptor (CB1R) in the 3 acetyl pyridine (3AP) rat model of ataxia. The role of the CB1R was examined using three different doses of the CB1R agonist, WIN-55,212-2 (WIN; 0.1, 0.5, 1 mg/kg) administrated 30 min prior to 3AP (55 mg/kg, i.p.) which leads to motor impairment through destruction of the inferior olive. In some groups, the CB1R antagonist AM251 (1 mg/kg) was given in combination with WIN. Locomotor activity and motor coordination were impaired by 3AP, and the application of WIN did not ameliorate this effect. However, the abnormal gait, rearing and grooming caused by 3AP were prevented by co-administration of AM251 with WIN. While the addition of the CB1R antagonist improved some ataxic symptoms, there was no effect of AM251 on balance or locomotor activity when co-administrated with WIN. Behavioral testing indicated that not only did WIN fail to exert any protective effect on ataxic symptoms; it exacerbated ataxic symptoms, suggesting that CB1R agonists may not be the ideal therapeutic drug in this disorder. When taken together, the findings from the present study indicate that cannabinoid modulation of ataxia symptoms may not act solely through CB1Rs and other cannabinoid receptors should be considered in future studies.
AB - Cerebellar ataxia is a neurodegenerative disorder leading to severe motor incoordination. Recently, it has been suggested that cannabinoids play a role in modulating ataxic symptoms. To understand the possible therapeutic effect of cannabinoids for the management of cerebellar ataxia, we used cannabinoid agonist/antagonists to target the cannabinoid type 1 receptor (CB1R) in the 3 acetyl pyridine (3AP) rat model of ataxia. The role of the CB1R was examined using three different doses of the CB1R agonist, WIN-55,212-2 (WIN; 0.1, 0.5, 1 mg/kg) administrated 30 min prior to 3AP (55 mg/kg, i.p.) which leads to motor impairment through destruction of the inferior olive. In some groups, the CB1R antagonist AM251 (1 mg/kg) was given in combination with WIN. Locomotor activity and motor coordination were impaired by 3AP, and the application of WIN did not ameliorate this effect. However, the abnormal gait, rearing and grooming caused by 3AP were prevented by co-administration of AM251 with WIN. While the addition of the CB1R antagonist improved some ataxic symptoms, there was no effect of AM251 on balance or locomotor activity when co-administrated with WIN. Behavioral testing indicated that not only did WIN fail to exert any protective effect on ataxic symptoms; it exacerbated ataxic symptoms, suggesting that CB1R agonists may not be the ideal therapeutic drug in this disorder. When taken together, the findings from the present study indicate that cannabinoid modulation of ataxia symptoms may not act solely through CB1Rs and other cannabinoid receptors should be considered in future studies.
U2 - 10.1007/s00221-022-06415-6
DO - 10.1007/s00221-022-06415-6
M3 - Journal article
C2 - 35859208
VL - 240
SP - 2339
EP - 2348
JO - Experimental Brain Research
JF - Experimental Brain Research
SN - 0014-4819
ER -
ID: 314571733