Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1 receptor

被引:6
|
作者
Belen Occhieppo, Victoria [1 ]
Martin Basmadjian, Osvaldo [1 ]
Andrea Marchese, Natalia [2 ,3 ]
Jaime, Andrea [1 ]
Fernanda Perez, Mariela [1 ]
Baiardi, Gustavo [4 ]
Bregonzio, Claudia [1 ]
机构
[1] Univ Nacl Cordoba, Fac Ciencias Quim, Inst Farmacol Expt Cordoba IFEC CONICET, Dept Farmacol, Haya de la Torre S-N, Cordoba, Argentina
[2] Univ Nacl Cordoba, Fac Ciencias Quim, Ctr Invest Quim Biol Cordoba CIQUIBIC, CONICET, Cordoba, Argentina
[3] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Quim Biol Ranwel Caputto, Cordoba, Argentina
[4] Univ Nacl Cordoba, Univ Catolica Cordoba, Fac Ciencias Quim, Lab Neurofarmacol,IIBYT CONICET, Cordoba, Argentina
关键词
GABA; Parvalbumin; Positive signs; Negative signs; Cognitive deficit; ANTERIOR CINGULATE CORTEX; POSSIBLE ANIMAL-MODEL; COGNITIVE IMPAIRMENT; ANTAGONIST PREVENTS; NEGATIVE SYMPTOMS; INSULAR CORTEX; RAT BEHAVIOR; NEURONS; BRAIN; HYPOFUNCTION;
D O I
10.1016/j.bbr.2022.113809
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Schizophrenia is a chronic disease affecting 1% worldwide population, of which 30% are refractory to the available treatments: thus, searching for new pharmacological targets is imperative. The acute and repeated ketamine administration are validated preclinical models that recreate the behavioral and neurochemical features of this pathology, including the parvalbumin-expressing interneurons dysfunction. Angiotensin II, through AT(1) receptors (AT(1)-R), modulates the dopaminergic and GABAergic neurotransmission. We evaluated the AT(1)-R role in the long-term neuronal activation and behavioral alterations induced by repeated ketamine administration. Adult male Wistar rats received AT(1)-R antagonist candesartan/vehicle (days 1-10) and ketamine/saline (days 6-10). After 14 days of drug-free, neuronal activation and behavioral analysis were performed. Locomotor activity, social interaction and novel object recognition tests were assessed at basal conditions or after ketamine challenge. Immunostaining for c-Fos, GAD67 and parvalbumin were assessed after ketamine challenge in cingulate, insular, piriform, perirhinal, and entorhinal cortices, striatum, and hippocampus. Additionally, to evaluate the AT(1)-R involvement in acute ketamine psychotomimetic effects, the same behavioral tests were performed after 6 days of daily-candesartan and a single-ketamine administration. We found that ketamine-induced long-lasting schizophrenia-like behavioral alterations, and regional-dependent neuronal activation changes, involving the GABAergic neurotransmission system and the parvalbumin-expressing interneurons, were AT(1)-R-dependent. The AT(1)-R were not involved in the acute ketamine psychotomimetic effects. These results add new evidence to the wide spectrum of action of ketamine and strengthen the AT(1)-R involvement in endurable alterations induced by psychostimulants administration, previously proposed by our group, as well as their preponderant role in the development of psychiatric pathologies.
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页数:11
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