Effects of the acute administration of delta-opioid receptor ligands on the excitability of rat hippocampal glutamate and brainstem monoamine neurons in vivo

Abstract

It was previously reported that the delta opioid receptor (DOR) agonist SNC80 and antagonist naltrindole modulate the excitability of hippocampal glutamate neurons in primary cultures. The present study aimed to investigate the acute effects of these ligands on the firing activity of hippocampal cornu ammonis 1/3 (CA1/3) glutamate, dorsal raphe nucleus (DRN) serotonin (5-HT), locus coeruleus (LC) noradrenaline, and ventral tegmental area (VTA) dopamine neurons in in vivo conditions. Adult Wistar male rats were used. SNC80 and naltrindole were administered intravenously. Neuronal firing activity was assessed using extracellular single-unit electrophysiology. SNC80, administered first at 1-3 mg/kg, dose-dependently inhibited CA1/3 glutamate, DRN 5-HT, and VTA dopamine neurons. Naltrindole, administered at 1-3 mg/kg after SNC80, did not have any additional effect. Naltrindole, administered first at 1-3 mg/kg, stimulated DRN 5-HT neurons in a dose-dependent manner; this stimulation was dose-dependently reversed by 1-3 mg/kg of SNC80. SNC80 and naltrindole inhibited LC noradrenaline neurons when only they were co-administered at 3 mg/kg, and only when SNC80 was administered first. In conclusion, DOR ligands alter the firing activity of hippocampal glutamate and brainstem monoamine neurons in in vivo conditions. The psychoactive effects of DOR ligands, reported in previous studies, might be explained, at least in part, by their ability to modulate the firing activity of hippocampal glutamate and brainstem monoamine neurons.

Maternal treatment with a selective delta-opioid receptor agonist during gestation has a sex-specific pro-cognitive action in offspring: mechanisms involved

“…In agreement with our previous results (Csatlosova et al, 2021) there were no sex differences in the firing activity of 5-HT neurons. The characteristics of the firing activity of hippocampal glutamate and brainstem 5-HT and dopamine neurons in offspring of the control dams were similar to those observed in control animals in our previous studies without any behavioral testing (Grinchii et al, 2022;Grinchii et al, 2023). Even though in the present study behavioral tests were performed on the same animals before electrophysiological recordings, they are unlikely to affect the firing activity of the neurons.…”

“…There were 11 dams in each treatment group. The dose of SNC80 has been selected according to our previous dose-response study ( Grinchii et al, 2023 ). Similarly, the period of gestation was chosen according to previous experiments with antidepressant drug treatments during gestation ( Viñas-Noguera et al, 2022 ; Grinchii et al, 2024 ).…”

“…In vivo electrophysiological experiments described previously ( Dremencov et al, 2022 ; Grinchii et al, 2022 ; Dremencov et al, 2023 ; Grinchii et al, 2023 ) were performed in male and female adult offspring of the SNC80- and vehicle-treated dams 24 h following behavioral testing. Urethane (1.25 g/kg, intraperitoneally: i. p.) or chloral hydrate (0.4 g/kg, i. p) anesthesia was used in experiments aiming to assess the excitability of hippocampal glutamate and brainstem monoamine neurons, respectively.…”

“…The action potentials generated by Frontiers in Pharmacology frontiersin.org the neurons were recorded using the AD Instruments Extracellular Recording System (Dunedin, New Zealand). Glutamate neurons of the CA1/3, 5-HT neurons of the DRN, and dopamine neurons of the VTA were identified according to the waveform of their action potentials and the pattern of their generation (Figure 2), as explained in our previous works (Dremencov et al, 2022;Grinchii et al, 2022;Dremencov et al, 2023;Grinchii et al, 2023). During the experiment, the rats' body temperature was maintained at 37 °C with a heating pad (Gaymor Instruments, Orchard Park, NY, United States).…”