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. 2025 May 27.
doi: 10.1007/s00213-025-06808-9. Online ahead of print.

D2 receptor activation modulates NMDA receptor antagonist-enhanced high-frequency oscillations in the olfactory bulb of freely moving rats

Jacek Wróbel  1 , Daniel Krzysztof Wójcik  2 , Mark Jeremy Hunt  2
Affiliations

D2 receptor activation modulates NMDA receptor antagonist-enhanced high-frequency oscillations in the olfactory bulb of freely moving rats

Jacek Wróbel et al. Psychopharmacology (Berl). .

Abstract

Rationale: NMDA receptor antagonists, used to model psychotic-like states and treat depression, enhance the power of high-frequency oscillations (HFO) in many mammalian brain regions. In rodents, the olfactory bulb (OB) is a particularly important site for generating this rhythm. OB projection neurons express D1 and D2 receptors (D1R and D2R) which interact with NMDA receptors.

Objectives: The aim of this study was to explore the effect of dopamine (DA) signalling in the OB on MK801-enhanced HFO.

Methods: Local field potentials from the OB and locomotor activity were recorded in adult male freely moving rats. MK801 was injected systemically or infused locally to the OB. The effects of D1R and D2R agonists (SKF38393, quinpirole) and antagonists (SCH23390, eticlopride), administered systemically or locally to the OB, were examined on MK801-enhanced HFO. Effects of the antipsychotics risperidone and aripiprazole were also examined.

Results: Local infusion of MK801 enhanced HFO power in the OB to levels similar to those observed after systemic injection. Neither systemic nor local blockade of D1R or D2R affected the MK801-enhanced HFO, despite reductions in hyperlocomotion. However, direct (systemic and local) D2R, but not D1R, stimulation caused a short-lasting reduction of MK801-enhanced HFO power and longer lasting reduction in frequency. Risperidone, but not aripiprazole, reduced MK801-enhanced HFO frequency.

Conclusions: These results suggest that NMDA receptor antagonist-enhanced HFO in the OB is generated predominantly independently of DA influence, however exogenous stimulation of D2R can modulate this rhythm. A second, but not third generation antipsychotic reduced HFO frequency.

Keywords: Antipsychotics; Dopamine agonist; Dopamine antagonist; Dopamine receptor; HFO; Local infusion; MK801; NMDA receptor antagonist; Olfactory bulb; Oscillations.

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Conflict of interest statement

Declarations. Ethical Approval: All experiments were conducted in accordance with the European Directive 2010/63/EU on the protection of animals used for scientific purposes and were approved by the 1 st Local Ethics Committee for Animal Experiments in Warsaw, Poland. Consent to participate: Not applicable. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests. Conflict interest: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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