Modulatory effect of dopamine receptors on long-term potentiation in dorsal and ventral hippocampus in anesthetized kindled rats

Eur J Pharmacol. 2026 Feb 28:1016:178590. doi: 10.1016/j.ejphar.2026.178590. Epub 2026 Jan 21.

Abstract

The dopaminergic system acts as a crucial regulator of synaptic plasticity. Nonetheless, the exact role of dopamine receptors in modulating this process following seizure remains unclear. We investigated the role of dopamine receptors on synaptic plasticity in the dorsal and ventral hippocampal CA1 regions of PTZ-kindled rats. Following kindling induction with repeated PTZ (37.5 mg/kg), evoked field potentials were obtained from the CA1 region in response to Schaffer collateral stimulation in urethane-anesthetized (1.5 g/kg) rats. Quinpirole hydrochloride (D2-like receptor agonist, 2.5, 5, 10, and 20μg/2.5 μL) or SKF38393 hydrochloride (D1-like receptor agonist, 5 and 10 μg/μL) were microinjected into the lateral ventricle 30 or 25 min before long-term potentiation (LTP) induction, respectively. Haloperidol (D2-like receptor antagonist, 2 μg/μL) was administered 15 min prior to quinpirole hydrochloride. D2-like receptors activation had a dual effect on synaptic potentiation in control and kindled animals across both hippocampal regions. Quinpirole hydrochloride affected on synaptic plasticity in a U-shaped manner in control rats, while restored impaired LTP in kindled animals. Haloperidol inhibited theses effects in both groups, while SKF38393 had no impact on synaptic plasticity. These findings underscore the function of dopaminergic receptors in synaptic plasticity and their potential therapeutic implications for alleviating seizure-induced dysfunction.

Keywords: D2-like receptors; Epilepsy; Hippocampus; Long-term potentiation; Seizure; Synaptic plasticity.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Anesthesia
  • Animals
  • CA1 Region, Hippocampal* / drug effects
  • CA1 Region, Hippocampal* / physiology
  • Dopamine Agonists / pharmacology
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Hippocampus* / physiology
  • Kindling, Neurologic* / drug effects
  • Kindling, Neurologic* / physiology
  • Long-Term Potentiation* / drug effects
  • Male
  • Quinpirole / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2* / metabolism
  • Receptors, Dopamine* / metabolism

Substances

  • Dopamine Agonists
  • Quinpirole
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D1
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine