Gender-related differences in the effects of nitric oxide donors on neuroleptic-induced catalepsy in mice

Abstract

It has been suggested that nigrostriatal dopaminergic transmission is modulated by nitric oxide (NO). Since there is evidence that gonadal hormones can affect extrapyramidal motor behavior in mammals, we investigated the effects of isosorbide dinitrate (ISD), linsidomine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP), three pharmacologically different NO donors, on neuroleptic-induced catalepsy in 60-to 80-day-old male and female albino mice. Catalepsy was induced with haloperidol (1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Drugs (or appropriate vehicle) were injected ip 30 min before haloperidol, with each animal being used only once. ISD (5, 20 and 50 mg/kg) caused a dose-dependent inhibition of catalepsy in male mice (maximal effect 120 min after haloperidol: 64% inhibition). In the females only at the highest dose of ISD was an attenuation of catalepsy observed, which was mild and short lasting. SIN-1 (10 and 50 mg/kg) did not significantly affect catalepsy in female mice, while a significant attenuation was observed in males at the dose of 50 mg/kg (maximal inhibition: 60%). SNAP (20 mg/kg) significantly attenuated catalepsy in males 120 min after haloperidol (44% inhibition), but had no significant effect on females. These results basically agree with literature data showing that NO facilitates central dopaminergic transmission, although the mechanisms are not fully understood. They also reveal the existence of gender-related differences in this nitrergic modulation in mice, with females being less affected than males. Correspondence

Modulating Role of NO in Haloperidol-Induced Catalepsy

“…Some substances regarded as NO donors (L-arginine, isosorbide dinitrate, linsidomine, and S-nitro-N-acetylpenicillamin) can prevent the development of neuroleptic catalepsy; this effect is sex-dependent [15]. The behavioral effects of L-arginine (100 mg/kg) observed in our study are quite in line with previous data [12].…”

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

“…C57BL/6j 11 (Mabrouk et al, 2010;Shiozaki et al, 1999;Banerjee et al, 2012;Greenbaum et al, 2012;Cannella et al, 2015;Hagino et al, 2015;Celorrio et al, 2016;Koranda et al, 2016;Celorrio et al, 2017;Charvin et al, 2017;Cortés et al, 2017) BALB/cJ 4 (Atack et al, 2014;Shook et al, 2010;Striem et al, 1997;Ionov & Severtsev, 2012b) Others 40 (Greco et al, 2010;Mihara et al, 2007;Shiozaki et al, 1999;Himori et al, 1994;Kanda et al, 1994;Kinoshita et al, 1994;Haraguchi et al, 1996;Haraguchi et al, 1997;Kobayashi et al, 1997;Matsuo et al, 2000;Nasu et al, 2000;Wang et al, 2000;Araki et al, 2001;El Yacoubi et al, 2001;Xu et al, 2002;Karasawa et al, 2003;Pires et al, 2003;Tsujikawa et al, 2003;Stasi et al, 2006;Marazziti et al, 2007;Kasture, Barhate, et al, 2009;Ardayfio et al, 2010;Bateup et al, 2010;Fink-Jensen et al, 2011;Manikandaselvi et al, 2012;Golden et al, 2013;…”

“…Check the model for pathophysiological/ behavioral characteristics already established for parkinsonism 35 1981 and 2020 (Clark et al, 2009;Antkiewicz-Michaluk et al, 2000;Alvarez-Cervera et al, 2005;Colombo et al, 2013;Ionov & Pushinskaya, 2013;Makhija & Jagtap, 2014;Zolbanin et al, 2014;Melo-Thomas & Thomas, 2015;Tonelli et al, 2017;Ahmadi et al, 2018;Ionov et al, 2018;Barroca et al, 2019;Schallert & Teitelbaum, 1981;Fowler & Mortell, 1992;Hyde et al, 1995;Frank & Schmidt, 2003;Srinivasan & Schmidt, 2003a;Marchese et al, 2004;Riedinger et al, 2011;Chopde et al, 1995;Weihmuller et al, 1988a;Luthra et al, 2008;Mabrouk et al, 2010;Cannella et al, 2015;Hagino et al, 2015;Ionov & Severtsev, 2012b;Haraguchi et al, 1996;Haraguchi et al, 1997;Nasu et al, 2000;Pires et al, 2003;Ardayfio et al, 2010) Explore potential new pathophysiological/ behavioral characteristics for parkinsonism 49 1981 and 2019 (Greco et al, 2010;Scheel-Krüger & Magelund, 1981;Miwa et al, 1996;Maj et al, 1999;Vetulani et al, 2003;Konieczny et al, 2007;<...>…”

Acute effects of selective serotonin reuptake inhibitors on neuroleptic-induced catalepsy in mice

“…The phenomenon of cataleptic immobility induced in rodents by typical neuroleptics (e.g., haloperidol, chlorpromazine, fluphenazine) is a robust behavioral method for studying nigrostriatal function and its modulation by cholinergic, serotonergic, nitrergic, and other neurotransmitter systems (1,2). There is some evidence that agents able to potentiate neuroleptic-induced catalepsy in rodents can intensify extrapyramidal symptoms in Parkinson disease; alternatively, drugs which attenuate catalepsy might reduce (or, at least, not increase) the extrapyramidal signs (3,4).…”

“…Since i) gender-related differences seem to be a common feature in the pharmacological properties of several centrally active drugs (8,9); ii) there is evidence for sex differences in the serotonergic control of gonadotropins release (10), and iii) the extrapyramidal system is modulated by sex hormones (2,11), the animals were separated by sex in order to detect any effect of gender on SSRIs acting on extrapyramidal function.…”