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Inverse relationship of cannabimimetic (R+)WIN 55, 212 on behavior and seizure threshold during the juvenile period.
Pharmacol Biochem Behav 2012; 100(3):474-84PB

Abstract

Cannabinoids have anti-convulsant effects in both in vivo and in vitro models of status epilepticus. Since the development of spontaneous seizures and neuronal vulnerability are age-dependent, we hypothesized that the anti-convulsant effects of cannabimimetics are also age-dependent. We administered a single injection of varied doses of (R+)WIN 55,212 (0.5, 1, 5 mg/kg) to postnatal (P) day 20 rats 90 min prior to induction of kainate (KA)-induced status epilepticus. The highest dose of (R+)WIN 55,212 (5 mg/kg) resulted in rapid onset of behavioral stupor, loss of balance, stiffening and immobility while standing on hind legs or laying flat in prone position; lower doses had minimal or no behavioral effect. After KA administration, seizure scores and electroencephalography (EEG) recordings were inversely related to (R+)WIN 55,212 dosage whereby higher doses were associated with high seizures scores and synchronous epileptiform activity and low doses with low seizure scores and diminished spiking in the EEG. Immunohistochemistry revealed a dose-dependent reduction in CB1 receptor expression with increasing concentrations of (R+)WIN 55,212 in presence or absence of KA seizures. Nissl and NeuN staining showed hippocampal injury was attenuated only when seizures were mild following low doses of WIN 55,212 (0.5, 1 mg/kg), consistent with the level of CB1 expression. Since low doses abolished seizures without psychotropic side-effects further study may facilitate a groundbreaking cannabamimetic therapeutic strategy to treat early-life seizures. Higher doses had adverse effects on behavior and failed to prevent seizures and protect CA1 neurons possibly due to inactivation or loss of CB1 receptors.

Authors+Show Affiliations

New York College of Osteopathic Medicine, Old Westbury, NY 11568, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22019959

Citation

Rudenko, V, et al. "Inverse Relationship of Cannabimimetic (R+)WIN 55, 212 On Behavior and Seizure Threshold During the Juvenile Period." Pharmacology, Biochemistry, and Behavior, vol. 100, no. 3, 2012, pp. 474-84.
Rudenko V, Rafiuddin A, Leheste JR, et al. Inverse relationship of cannabimimetic (R+)WIN 55, 212 on behavior and seizure threshold during the juvenile period. Pharmacol Biochem Behav. 2012;100(3):474-84.
Rudenko, V., Rafiuddin, A., Leheste, J. R., & Friedman, L. K. (2012). Inverse relationship of cannabimimetic (R+)WIN 55, 212 on behavior and seizure threshold during the juvenile period. Pharmacology, Biochemistry, and Behavior, 100(3), pp. 474-84. doi:10.1016/j.pbb.2011.10.005.
Rudenko V, et al. Inverse Relationship of Cannabimimetic (R+)WIN 55, 212 On Behavior and Seizure Threshold During the Juvenile Period. Pharmacol Biochem Behav. 2012;100(3):474-84. PubMed PMID: 22019959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inverse relationship of cannabimimetic (R+)WIN 55, 212 on behavior and seizure threshold during the juvenile period. AU - Rudenko,V, AU - Rafiuddin,A, AU - Leheste,J R, AU - Friedman,L K, Y1 - 2011/10/12/ PY - 2011/02/15/received PY - 2011/09/26/revised PY - 2011/10/02/accepted PY - 2011/10/25/entrez PY - 2011/10/25/pubmed PY - 2012/5/5/medline SP - 474 EP - 84 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 100 IS - 3 N2 - Cannabinoids have anti-convulsant effects in both in vivo and in vitro models of status epilepticus. Since the development of spontaneous seizures and neuronal vulnerability are age-dependent, we hypothesized that the anti-convulsant effects of cannabimimetics are also age-dependent. We administered a single injection of varied doses of (R+)WIN 55,212 (0.5, 1, 5 mg/kg) to postnatal (P) day 20 rats 90 min prior to induction of kainate (KA)-induced status epilepticus. The highest dose of (R+)WIN 55,212 (5 mg/kg) resulted in rapid onset of behavioral stupor, loss of balance, stiffening and immobility while standing on hind legs or laying flat in prone position; lower doses had minimal or no behavioral effect. After KA administration, seizure scores and electroencephalography (EEG) recordings were inversely related to (R+)WIN 55,212 dosage whereby higher doses were associated with high seizures scores and synchronous epileptiform activity and low doses with low seizure scores and diminished spiking in the EEG. Immunohistochemistry revealed a dose-dependent reduction in CB1 receptor expression with increasing concentrations of (R+)WIN 55,212 in presence or absence of KA seizures. Nissl and NeuN staining showed hippocampal injury was attenuated only when seizures were mild following low doses of WIN 55,212 (0.5, 1 mg/kg), consistent with the level of CB1 expression. Since low doses abolished seizures without psychotropic side-effects further study may facilitate a groundbreaking cannabamimetic therapeutic strategy to treat early-life seizures. Higher doses had adverse effects on behavior and failed to prevent seizures and protect CA1 neurons possibly due to inactivation or loss of CB1 receptors. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/22019959/Inverse_relationship_of_cannabimimetic__R+_WIN_55_212_on_behavior_and_seizure_threshold_during_the_juvenile_period_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(11)00327-3 DB - PRIME DP - Unbound Medicine ER -