Altered Intracellular Signaling Associated with Dopamine D2 Receptor in the Prefrontal Cortex in Wistar Kyoto Rats

Korlatowicz, Agata; Kolasa, Magdalena; Pabian, Paulina; Solich, Joanna; Latocha, Katarzyna; Dziedzicka-Wasylewska, Marta; Faron-Górecka, Agata

doi:10.3390/ijms24065941

Cited by 4 publications

(1 citation statement)

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“…In addition, the WKY rats show hypoactivity in open field tests, high anxiety (Dugovic et al, 2000) and depressive behaviour (Pare, 1992, 1994). Of particular relevance to the present study, there are significant differences in dopamine transporter expression in the nucleus accumbens and VTA of WKY rats compared to Wistar and SD strains (Jiao et al, 2003) and differences in dopamine receptor expression (Korlatowicz et al, 2023; Morganstern & Tejani‐Butt, 2010; Yaroslavsky et al, 2006). These behavioural and neurochemical characteristics make WKY unsuitable as a reference strain in the current study.…”

Section: Discussionmentioning

confidence: 71%

Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate

Li,

Huang,

Chen

et al. 2024

Eur J of Neuroscience

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The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention‐deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast‐scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward‐predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low‐dose methylphenidate in ADHD.

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Section: Discussionmentioning

confidence: 71%

Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate

Li,

Huang,

Chen

et al. 2024

Eur J of Neuroscience

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Unraveling psilocybin’s therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression

Kolasa,

Nikiforuk,

Korlatowicz

et al. 2024

Psychopharmacology

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Rationale Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects. Objectives We set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST). Our secondary objectives involved exploring strain-specific alterations in neuroplasticity-related parameters, including brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc). Methods Conducting post-acute and extended assessments after a single PSI administration, we applied behavioral tests and biochemical analyses to measure serum BDNF levels and neuroplasticity-related parameters in the prefrontal cortex. Statistical analyses were deployed to discern significant differences between the rat strains and assess the impact of PSI on behavioral and biochemical outcomes. Results Our findings uncovered significant behavioral disparities between WKY and WIS rats, indicating passive behavior and social withdrawal in the former. PSI demonstrated pronounced pro-social and antidepressant effects in both strains, each with its distinctive temporal trajectory. Notably, we identified strain-specific variations in BDNF-related signaling and observed the modulation of Arc expression in WKY rats. Conclusions Our study delineated mood-related behavioral nuances between WKY and WIS rat strains, underscoring the antidepressant and pro-social properties of PSI in both groups. The distinct temporal patterns of observed changes and the identified strain-specific neuroplasticity alterations provide valuable insights into the TRD phenotype and the mechanisms underpinning the efficacy of PSI.

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Preclinical models of treatment-resistant depression: challenges and perspectives

Kolasa,

Faron-Górecka

2023

Pharmacol. Rep

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Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD model is the lack of response to at least two attempts at antidepressant pharmacotherapy. The causes of TRD are not known; nevertheless, it is estimated that even 60% of TRD patients are so-called pseudo-TRD patients, in which multiple biological factors, e.g., gender, age, and hormonal disturbances are concomitant with depression and involved in antidepressant drug resistance. Whereas the phenomenon of TRD is a complex disorder difficult to diagnose and successfully treat, the search for new treatment strategies is a significant challenge of modern pharmacology. It seems that despite the complexity of the TRD phenomenon, some useful animal models of TRD meet the construct, the face, and the predictive validity criteria. Based on the literature and our own experiences, we will discuss the utility of animals exposed to the stress paradigm (chronic mild stress, CMS), and the Wistar Kyoto rat strain representing an endogenous model of TRD. In this review, we will focus on reviewing research on existing and novel therapies for TRD, including ketamine, deep brain stimulation (DBS), and psychedelic drugs in the context of preclinical studies in representative animal models of TRD.

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Altered Intracellular Signaling Associated with Dopamine D2 Receptor in the Prefrontal Cortex in Wistar Kyoto Rats

Cited by 4 publications

References 50 publications

Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate

Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate

Unraveling psilocybin’s therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression

Preclinical models of treatment-resistant depression: challenges and perspectives

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