Research Article

Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats

Volume: 22 Number: 2 June 27, 2025

Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats

Abstract

Schizophrenia is a severe psychiatric disorder with about 1% prevalance. NMDA receptor antagonists such as Phencyclidine (PCP) and MK-801 are commonly used for modeling schizophrenia in rodents. In literature, despite of the concensus about subchronic PCP administration (commonly 7 days, bi-daily administration followed by a 1 week washout period), there are different subchronic administration regimens for MK-801 beside 7 days, bidaily (MK-801-7), such as 14 days (MK-801-14) daily or 28 days daily injections. In this study, we aimed to compare two prevalant MK-801 models (MK-801-7 and MK-801-14, 0.2 mg/kg) in both behavioural and molecular changes. Wistar Hannover rats grouped as control (n=10), MK-801-14 (n=8) and MK-801-7 (n=8). Prepulse inhibition of acustic startle response (PPI), novel object recognition test (NORT), social interaction (SI) and Morris's water maze (MWM) tests were used for behavioural analyzes while real time polimerase chain reaction (Rt-PCR) was conducted for molecular analyzes of glutamic acid decarboxilase 67 (GAD67) and parvalbumin. Our results showed decreased PPI in MK-801-14 and MK801-7 groups. Moreover, in both models platform finding latencies were increased and swimming time in platform area was decreased in MWM. MK-801-14 and MK-801-7 reduced following and raised avoiding behaviours in SI. In Rt-PCR, GAD67 mRNA levels were decreased by MK-801-14 and MK-801-7 administrations. However, only MK-801-7 decreased discrimination index in NORT and parvalbumin mRNA levels. In this study, it has been showed that although MK-801-14 and MK-801-7 administrations revealed smiliar schizophrenia like symptoms in rats, MK-801-7 has partial superiories in certain aspects.

Keywords

References

  1. [1] Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, "just the facts" what we know in 2008. 2. Epidemiology and etiology. Schizophr Res. 2008; 102(1-3): 1-18.
  2. [2] Schwartz TL, Sachdeva S, Stahl SM. Glutamate neurocircuitry: theoretical underpinnings in schizophrenia. Front Pharmacol. 2012; 3: 195.
  3. [3] Snigdha S, Neill JC. Efficacy of antipsychotics to reverse phencyclidine-induced social interaction deficits in female rats--a preliminary investigation. Behav Brain Res. 2008; 187(2): 489-494.
  4. [4] Lahti AC, Weiler MA, Tamara M, Parwani A, Tamminga CA. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology. 2001; 25(4): 455-467.
  5. [5] Akbarian S, Sucher N, Bradley D, Tafazzoli A, Trinh D, Hetrick WP, Potkin SG, Sandman CA, Bunney WE Jr, Jones EG. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci. 1996; 16(1): 19-30.
  6. [6] Kristiansen L, Beneyto M, Haroutunian V, Meador-Woodruff J. Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia. Mol Psychiatry. 2006; 11(8): 737-747.
  7. [7] Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005; 6(4): 312-324.
  8. [8] Lewis DA, Curley AA, Glausier JR, Volk DW. Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci. 2012; 35(1): 57-67.

Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Research Article

Publication Date

June 27, 2025

Submission Date

January 17, 2018

Acceptance Date

February 25, 2018

Published in Issue

Year 2018 Volume: 22 Number: 2

APA
Ünal, G., & Arıcıoğlu, F. (2025). Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats. Journal of Research in Pharmacy, 22(2), 199-208. https://izlik.org/JA58WZ56LP
AMA
1.Ünal G, Arıcıoğlu F. Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats. J. Res. Pharm. 2025;22(2):199-208. https://izlik.org/JA58WZ56LP
Chicago
Ünal, Gökhan, and Feyza Arıcıoğlu. 2025. “Comparison of Behavioural and Molecular Effects of Two Different Schizophrenia Models Induced by Subchronic MK-801 Administration in Rats”. Journal of Research in Pharmacy 22 (2): 199-208. https://izlik.org/JA58WZ56LP.
EndNote
Ünal G, Arıcıoğlu F (June 1, 2025) Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats. Journal of Research in Pharmacy 22 2 199–208.
IEEE
[1]G. Ünal and F. Arıcıoğlu, “Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats”, J. Res. Pharm., vol. 22, no. 2, pp. 199–208, June 2025, [Online]. Available: https://izlik.org/JA58WZ56LP
ISNAD
Ünal, Gökhan - Arıcıoğlu, Feyza. “Comparison of Behavioural and Molecular Effects of Two Different Schizophrenia Models Induced by Subchronic MK-801 Administration in Rats”. Journal of Research in Pharmacy 22/2 (June 1, 2025): 199-208. https://izlik.org/JA58WZ56LP.
JAMA
1.Ünal G, Arıcıoğlu F. Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats. J. Res. Pharm. 2025;22:199–208.
MLA
Ünal, Gökhan, and Feyza Arıcıoğlu. “Comparison of Behavioural and Molecular Effects of Two Different Schizophrenia Models Induced by Subchronic MK-801 Administration in Rats”. Journal of Research in Pharmacy, vol. 22, no. 2, June 2025, pp. 199-08, https://izlik.org/JA58WZ56LP.
Vancouver
1.Gökhan Ünal, Feyza Arıcıoğlu. Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats. J. Res. Pharm. [Internet]. 2025 Jun. 1;22(2):199-208. Available from: https://izlik.org/JA58WZ56LP