# Involvement of D1- and D2-like dopamine receptors in the hippocampal CA1 region in mediating the restraint stress-induced analgesia in the rats

**Authors:** Diba Shirmohammadi, Homayoon Golmohammadi, Shima Abtin, Abbas Haghparast

PMC · DOI: 10.1016/j.ibneur.2026.02.016 · 2026-02-21

## TL;DR

This study shows that dopamine receptors in the rat hippocampus are involved in pain relief caused by psychological stress.

## Contribution

The study identifies the role of D1- and D2-like dopamine receptors in the hippocampal CA1 region in mediating stress-induced analgesia.

## Key findings

- High doses of SCH23390 and sulpiride reduced restraint stress-induced analgesia in rats.
- Estimated ED50 values suggest both D1-like and D2-like receptors contribute to the analgesic effects of restraint stress.

## Abstract

Acute stress exposure can elicit analgesic responses in multiple pain models. Research indicates that dopaminergic pathways in the hippocampus contribute to the analgesic responses elicited by forced swim stress, considered a combination of physical and psychological stress. Since psychological and physical stresses can trigger different brain pathways and areas, this study has examined how dopaminergic receptors in the CA1 region of the hippocampus affect the pain relief induced by restraint stress (RS), generally considered a psychological stress, in an acute pain model. Ninety-six Wistar rats underwent stereotaxic surgery, during which a cannula was unilaterally implanted in the CA1 region of the hippocampus. Five minutes prior to exposure to RS, D1- and D2-like dopamine receptor antagonists (SCH23390 and sulpiride, respectively) or their respective carriers, saline and DMSO, were administered in different doses (0.25, 1, and 4 µg/0.5 µl per rat) into the CA1 area. The analgesic effects of RS were examined with and without dopaminergic receptor antagonists using the tail-flick test. This study's findings indicated that the administration of SCH23390 and sulpiride into the CA1 area of the hippocampus at the maximal doses (4 µg/0.5 µl; P < 0.001) markedly diminished the analgesic benefits of RS in the acute pain paradigm. The magnitude of estimated ED50s in the effect of these antagonists on reducing the RS-induced analgesia was 1.64 µg for SCH23390 and 2.79 µg for sulpiride, suggesting that both dopamine D1-like and D2-like receptors in the CA1 region of the hippocampus likely contribute to the analgesic effects of RS in the rats.

## Linked entities

- **Chemicals:** SCH23390 (PubChem CID 5018), sulpiride (PubChem CID 5355), saline (PubChem CID 5234), DMSO (PubChem CID 679)

## Full-text entities

- **Diseases:** pain (MESH:D010146), analgesia (MESH:D000699), acute pain (MESH:D059787)
- **Chemicals:** dopaminergic receptor antagonists (-), DMSO (MESH:D004121), sulpiride (MESH:D013469), SCH23390 (MESH:C534628)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12973749/full.md

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Source: https://tomesphere.com/paper/PMC12973749