Deneysel Şizofreni Modelleri

Yıl 2015, , 12 - 20, 30.09.2015

Oğuz Mutlu , Havva Kaya

https://doi.org/10.30934/kusbed.349516

Öz

Şizofreni deney hayvanlarında gerçek anlamda modellenemeyen yegane insan hastalığı olarak tartışılabilir. Deney
hayvanlarında insanlardaki gibi düşüncenin konuşularak ifade edilmesi yeteneği olmaması araştırmalar için gerekli
yeterliliğe sahip bir şizofreni modeli oluşturulmasına engel olmaktadır. Ancak, deney hayvanlarında şizofreninin
fizyopatolojisini ve şizofreni tedavisinde kullanılan veya kullanım potansiyeli olan yeni ilaçların etkilerini
değerlendirmeye olanak veren bazı modeller sınırlı bir yeterlilikle de olsa kullanılmaya çalışılmaktadır. Bunlardan
bazıları lokomosyon ve stereotipi modelleri, koşullanmış sakınma cevabı, katatoni testi, sıçan pençe testi, kendini
uyarma paradigmaları, ürkme refleksinin zayıf bir ön uyarı aracılığı ile inhibisyonu, latent inhibisyon paradigmaları,
rodentlerde sosyal etkileşme testi ile şizofreninin değerlendirilmesi, bilişsel modeller, hücresel ve moleküler
modeller, farmakolojik modeller, gelişimsel modeller, genetik modeller olarak sınıflandırılabilir. 

Anahtar Kelimeler

Şizofreni, hayvan modelleri, antipsikotikler

Experimental Schizophrenia Models

Öz

Schizophrenia is a unique disease which cannot be mimicked exactly in experimental animals. In experimental
animals, the thoughts cannot be explained by talking like in men and this causes it difficult to form a sufficient
schizophrenia model in experimental investigations. However, some models were used to investigate the effects of
new drugs in the therapy of schizophrenia and in the physiopathology of schizophrenia. Some of these models can be
classified as locomotion and stereotype models, conditioned avoidance responding, catalepsy test, rat paw test, selfstimulation
paradigms, prepulse inhibition of the startle reflex, latent inhibition paradigms, evaluating schizophrenia
by social interaction test in rodents, cognitive models, cellular and molecular models, pharmacological models,
developmental models, genetic models. 

Anahtar Kelimeler

Schizophrenia, animal models, antipsychotics

Kaynakça

• Segal DS, Geyer MA, Schuckit A. Stimulant-induced psychosis: an evaluation of animal models. In: Youdim MBH, Lovenberg W, Sharman DF ve diğ. Essays in neurochemistry and neuropharmacology. John Wiley and Sons, New York, 1981: 95–130.
• Snyder S. Amphetamine psychosis: a ‘‘model’’ schizophrenia mediated by catecholamines. Am J Psychiatry.1973; 130: 61–67.
• Kuribara H, Todokoro S. Correlation between anti avoidance activities of antipsychotic drugs in rats and daily clinical doses. Pharmacol Biochem Behav.1981; 14: 181-192.
• Sanger DJ. The effect of clozapine on shuttle box avoidance responding in rats: comparison with haloperidol and chlordiazaepoxide. Pharmacol Biochem Behav.1985; 23: 231-236.
• Sanberg PR, Bunsey MD, Giordano M ve diğ. The catalepsy test: its ups and downs. Behav Neurosci.1988; 102: 748-759.
• Ellenbroek BA, Peeters BW, Honig WM ve diğ. The paw test: a behavioural paradigm for differentiating between classical and atypical neuroleptic drugs. Psychopharmacology.1987; 93: 343-348.
• Roberts DCS, Vickers G. Atypical neuroleptics increase self-administration of cocaine: an evaluation of a behavioural screen for antipsychotic activity. Psychopharmacology.1984; 82: 135-139.
• Geyer MA, Braff DL. Startle habituation and sensorimotor gating in schizophrenia and related animal models. Schizophr Bull. 1987; 13: 643–668.
• Taiminen T, Jaaskelainen S, Ilonen T ve diğ. Habituation of the blink reflex in first-episode schizophrenia, psychotic depression and non-psychotic depression. Schizophr Res. 2000; 44: 69–79.
• Swerdlow NR, Geyer MA. Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull.1998; 24: 285–301.
• Wilkinson LS, Killcross SS, Humby T ve diğ. Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response with disrupting latent inhibition. Neuropsychopharmacology. 1994; 10: 61-72.
• Lubow RE. Latent inhibition. Psychol Bull.1973; 79: 398-407.
• Christison GW, Atwater GE, Dunn LA ve diğ. Haloperidol enhancement of latent inhibition: relation to therapeutic action? Biol Psychiatry.1988; 23: 746-749.
• Trimble KM, Bell R, King DJ. Enhancement of latent inhibition in the rat by the atypical antipsychotic agent remoxipride. Pharmacol Biochem Behav.1997; 56: 809-816.
• Corbett R, Hartman H, Kerman LL ve diğ. Effects of atypical antipsychotic agents on social behavior in rodents. Pharmacol Biochem Behav.1993; 45: 9-17.
• Kuppinger HE, Harrington A, Kaczmarek MJ ve diğ. The effects of phencyclidine and amphetamine on social behavior in tether-restrained and freely moving rats. Exp Clin Psychopharmacol.1996; 4: 77-81.
• Sams-Dodd F. Effect of novel antipsychotic drugs on phencyclidine-induced stereotyped behavior and social interaction test. Behav Pharmacol.1997; 8: 196-215.
• Goldberg TE, Gold JM, Braff DL. Neuropsychological functioning and time-linked information processing is schizophrenia. RevPsychiatry.1991; 10: 60–78.
• Hoff AL, Faustman WO, Wieneke M ve diğ. The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology.1996;15: 361–369.
• Ragozzino M, Wilcox C, Raso M ve diğ. Involvement of rodent prefrontal cortex subregions in strategy switching. BehavNeurosci.1999; 113: 32–41.
• Robbins T, Everitt B, Marston H ve diğ. Comparative effects of ibotenic acid- and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes. BehavBrain Res.1989; 35: 221–240.
• Ellenbroek B, Cools A. Animal models with construct validity for schizophrenia. BehavPharmacol.1990; 1: 469–490.
• Benes FM, McSparren J, Bird ED ve diğ. Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry. 1991; 48: 996–1001.
• Lieberman JA, Sheitman BB, Kinon BJ. Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology.1997; 17: 205–229.
• Creese I. Stimulants: neurochemical, behavioral, and clinical perspectives. New York: Raven Press. 1983.
• Geyer MA, Braff DL, Swerdlow NR. Startle-response measures of information processing in animals: relevance to schizophrenia. In: Haug M, Whalen RE, eds. Animal models of human emotion and cognition. Washington, DC: APA Books, 1999: 103–116.
• Weike AI, Bauer U, Hamm AO. Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients. Biol Psychiatry. 2000; 47: 61–70.
• Bowers M, Freedman D. ‘‘Psychedelic’’ experiences in acute psychosis. Arch Gen Psychiatry.1966; 15.
• Hollister LE. Chemical psychoses: LSD and related drugs. Springfield, IL: Charles C Thomas Publisher, 1968.
• Weil-Malherbe H, Szara SI. The biochemistry of functional and experimental psychoses. Springfield, IL: Charles C Thomas Publisher, 1971.
• Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D- 2 and serotonin-2 pKi values. J Pharmacol Exp Ther.1989; 251: 238–246.
• Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991; 148: 1301–1308.
• Sams-Dodd R. Phencyclidine-induced stereotyped behaviour and social isolation in the rat: a possible animal model of schizophrenia. BehavPharmacol.1996; 7: 3–23.
• Jentsch JD, Redmond DE Jr, Elsworth JD ve diğ. Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine. Science. 1997; 277: 953–955.
• Lipska BK, Weinberger DR. Delayed effects of neonatal hippocampal damage on haloperidol-induced catalepsy and apomorphine- induced stereotypic behaviors in the rat. Brain Res Dev Brain Res.1993; 75: 213–222.
• Lipska BK, Weinberger DR. To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology. 2000; 23: 223–239.
• Acri JB, Brown KJ, Saah MI ve diğ. Strain and age differences in acoustic startle responses and effects of nicotine in rats. Pharmacol Biochem Behav.1995; 50: 191-198.
• Lipska BK, Weinberger DR. Genetic variation in vulnerability to the behavioral effects of neonatal hippocampal damage in rats. Proc Natl Acad Sci USA.1995; 92: 8906-8910.
• Kolakowska T, Williams AO, Arden M ve diğ. Schizophrenia with good and poor outcome. I:early clinical features, response to neuroleptics and signs of organic dysfunction. Br J Psychiatr.1985;146: 229-239.