D2 dopamine and CB2 cannabinoid receptor cooperation restores striatal LTP in an epilepsy model
6 affiliations
- 1Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia 06132, Italy
- 2Section of Physiology and Biochemistry, Department of Medicine and Surgery, University of Perugia, Perugia 06132, Italy
- 3Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia 06132, Italy; Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia 06132, Italy
- 4Department of Pharmacological and Biomolecular Sciences, University of Milano, Milan, Italy
- 5Laboratory of Neurology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain
- 6Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia 06132, Italy
Abstract
Increasing evidence suggests that subcortical structures contribute to seizure susceptibility and cognitive impairment in several epileptic syndromes. However, research into mechanisms linking neuronal excitability and synaptic dysfunction in epilepsy has mainly focused on the cortex and hippocampus, leaving basal ganglia contributions largely unexplored. Using a genetic murine model of Lafora disease (LD), a drug-resistant form of neurodegenerative epilepsy, we performed ex vivo patch-clamp recordings to assess neuronal excitability, synaptic transmission, and plasticity of striatal medium spiny neurons. Our results reveal progressive alterations in corticostriatal transmission and long-term synaptic plasticity, including long-term potentiation (LTP). Electrophysiological and biochemical assessments showed a reduced NMDA/AMPA ratio and reduced expression of NMDA receptor subunits and dopamine receptors in striatal neurons of LD mice. Exposure to a dopamine D2 receptor agonist and to cannabidiol restored long-term plasticity in LD mice, suggesting a D2R- and CB2R-dependent synergic action on striatal LTP. Our findings highlight basal ganglia dysfunction in experimental epilepsy and suggest an unconventional dopaminergic-endocannabinoid interplay.
Related
- Striatal M4 Receptors Mediate M4 PAM Antipsychotic-like Efficacy Independently of Normalizing Striatal Dopamine Release
- The effects of use of medications on striatal dopamine transporter binding assessed by [123I]I-FP-CIT SPECT in patients with Parkinson’s disease from the PPMI cohort
- Cannabinoid CB1 Receptor Regulates Spinal Dorsal Horn Synaptic Plasticity in a Mouse Model of Neuropathic Pain through the CB1R/SREBP1/NAMPT/SIRT1 Metabolic Regulatory Framework
- Efficacy profiling of structurally diverse cannabinoid receptor ligands across transducer-coupling assays
- Integrated pharmacological and structural profiling reveals CB1 residue interaction patterns associated with synthetic cannabinoid receptor agonist efficacy
BibTeX
@article{sciaccaluga2026dopamine,
title = {{D2 dopamine and CB2 cannabinoid receptor cooperation restores striatal LTP in an epilepsy model}},
author = {Miriam Sciaccaluga and Laura Bellingacci and Valentina Imperatore and Anna Aurora Taddei and Alessandro Tozzi and Massimiliano Di Filippo and Marta Barzasi and Fabrizio Gardoni and Marina P. Sánchez and José M. Serratosa and Lucilla Parnetti and Andrea Mancini and Cinzia Costa},
journal = {Neurobiology of Disease},
year = {2026},
month = oct,
doi = {10.1016/j.nbd.2026.107648},
url = {https://doi.org/10.1016/j.nbd.2026.107648},
note = {CC BY},
}
RIS
TY - JOUR
TI - D2 dopamine and CB2 cannabinoid receptor cooperation restores striatal LTP in an epilepsy model
AU - Miriam Sciaccaluga
AU - Laura Bellingacci
AU - Valentina Imperatore
AU - Anna Aurora Taddei
AU - Alessandro Tozzi
AU - Massimiliano Di Filippo
AU - Marta Barzasi
AU - Fabrizio Gardoni
AU - Marina P. Sánchez
AU - José M. Serratosa
AU - Lucilla Parnetti
AU - Andrea Mancini
AU - Cinzia Costa
PY - 2026
DA - 2026/10/30
JO - Neurobiology of Disease
DO - 10.1016/j.nbd.2026.107648
UR - https://doi.org/10.1016/j.nbd.2026.107648
AB - Increasing evidence suggests that subcortical structures contribute to seizure susceptibility and cognitive impairment in several epileptic syndromes. However, research into mechanisms linking neuronal excitability and synaptic dysfunction in epilepsy has mainly focused on the cortex and hippocampus, leaving basal ganglia contributions largely unexplored. Using a genetic murine model of Lafora disease (LD), a drug-resistant form of neurodegenerative epilepsy, we performed ex vivo patch-clamp recordings to assess neuronal excitability, synaptic transmission, and plasticity of striatal medium spiny neurons. Our results reveal progressive alterations in corticostriatal transmission and long-term synaptic plasticity, including long-term potentiation (LTP). Electrophysiological and biochemical assessments showed a reduced NMDA/AMPA ratio and reduced expression of NMDA receptor subunits and dopamine receptors in striatal neurons of LD mice. Exposure to a dopamine D2 receptor agonist and to cannabidiol restored long-term plasticity in LD mice, suggesting a D2R- and CB2R-dependent synergic action on striatal LTP. Our findings highlight basal ganglia dysfunction in experimental epilepsy and suggest an unconventional dopaminergic-endocannabinoid interplay.
SN - 1095-953X
SN - 0969-9961
ER -