Wistar Kyoto rats exhibit decreased serotonin neuronal firing and increased norepinephrine burst activity but dampened hippocampal α2-adrenoceptor sensitivity

J Psychopharmacol. 2023 Nov;37(11):1105-1115. doi: 10.1177/02698811231209235. Epub 2023 Nov 9.

Abstract

Background: Wistar Kyoto (WKY) rats manifest abnormalities in the function of monoamine receptors and transporters, as well as levels of these neurotransmitters in the brain. The present study assessed alterations in the firing activity of serotonin (5-hydroxytryptamine [5-HT]), norepinephrine (NE), and dopamine (DA) neurons, as well as the activity of 5-HT and NE receptors and transporters in the hippocampus.

Methods: In vivo electrophysiological recordings were conducted in male WKY and Wistar rats. Extracellular single-unit recordings of 5-HT, NE, and DA neurons were performed. Recordings of pyramidal neurons were conducted in the medial prefrontal cortex (mPFC) and the hippocampus, where direct application of 5-HT and NE by iontophoresis was also carried out.

Results: The mean firing rate of 5-HT neurons was significantly decreased in WKY compared to Wistar rats. The burst activity of NE neurons was significantly increased in WKY, while their mean firing activity was not changed. There was no alteration in the firing, burst, and population activity of DA neurons in WKY animals. In the hippocampus, a decrease in sensitivity of α2-adrenoceptors, but not 5-HT receptors, was observed. There was, however, no change in the activity of 5-HT and NE transporters. The firing activity of mPFC pyramidal neurons was similar in WKY versus Wistar rats.

Conclusion: In WKY rats, there was a decrease in the firing activity of 5-HT neurons. There was also an enhanced burst activity of NE neurons, accompanied by a reduction in sensitivity of the α2-adrenoceptor in the hippocampus, inferring a decrease in NE transmission.

Keywords: Wistar Kyoto; depression; dopamine; electrophysiology; norepinephrine; serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus / physiology
  • Male
  • Neurons
  • Norepinephrine*
  • Rats
  • Rats, Inbred WKY
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Adrenergic
  • Serotonin* / physiology

Substances

  • Serotonin
  • Norepinephrine
  • Receptors, Adrenergic

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