Influence of aversive stimulation on haloperidol-induced catalepsy in rats

Abstract

Catalepsy – an immobile state in which individuals fail to change imposed postures – can be induced by haloperidol. In rats, the pattern of haloperidol-induced catalepsy is very similar to that observed in Parkinson’s disease (PD). As some PD symptoms seem to depend on the patient’s emotional state, and as anxiety disorders are common in PD, it is possible that the central mechanisms regulating emotional and cataleptic states interplay. Previously, we showed that haloperidol impaired contextual-induced alarm calls in rats, without affecting footshock-evoked calls. Here, we evaluated the influence of distinct aversive stimulations on the haloperidol-induced catalepsy. First, male Wistar rats were subjected to catalepsy tests to establish a baseline state after haloperidol or saline administration. Next, distinct cohorts were exposed to open-field; elevated plus-maze; open-arm confinement; inescapable footshocks; contextual conditioned fear; or corticosterone administration. Subsequently, catalepsy tests were performed again. Haloperidol-induced catalepsy was verified in all drug-treated animals. Exposure to open-field, elevated plus-maze, open-arm confinement, footshocks, or administration of corticosterone had no significant effect on haloperidol-induced catalepsy. Contextual conditioned fear, which is supposed to promote a more intense fear, increased catalepsy over time. Our findings suggest that only specific defensive circuitries modulate the nigrostriatal system mediating the haloperidol-induced cataleptic state.

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

“…Some studies have investigated, on the haloperidol‐induced catalepsy model, characteristics already established for PD, such as the relationship between motor and non‐motor symptoms, exploring, for example, the interactions between fear/anxiety and the cataleptic state. The results of these studies reinforce the clinical relationship suggested between PD and anxiety disorders (Barroca et al., 2019; Colombo et al., 2013). Others are investigating paradoxical kinesia—the sudden ability of PD patients to perform motor tasks depending on external factors.…”

“…Most studies (85.49% of the 255 studies included in our review) did not carry out a specific analysis of the temporal evolution of the haloperidol effect on catalepsy. Among the studies that performed a temporal analysis, some degree of catalepsy could be observed after 30 min of administration (Barroca et al., 2019; Beurrier et al., 2009; Colombo et al., 2013; Parambi et al., 2020). A consistent catalepsy induction often appears from 60 min (Darbaky et al., 2003; Jena et al., 2014; Nuutila et al., 1987; Sharma et al., 2020) and could last up to 240–300 min after administration (Ardashov et al., 2011; Invernizzi et al., 2002; Ionov & Severtsev, 2012b; Moo‐Puc et al., 2003; Pavlova & Il’ina et al., 2014; Verhagen‐Kamerbeek et al., 1993).…”

“…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;<...>…”

Rodent Brain Pathology, Audiogenic Epilepsy

“…The freezing reactions which are induced either in nature, or as the result of direct brain stimulations could be related to abnormal brain state-catalepsy. The cataleptic state induced by haloperidol (modulating dopamine transmission) was shown to be sensitive to aversive stimulations [ 50 ], and this type of cataleptic reactions could be modulated by changes in glutamatergic transmission in IC [ 51 ]. This could be regarded as the indication that cataleptic muscle tone pattern has probably some common links with the brain stem defense circuits.…”

Temporal Factors Modulate Haloperidol-Induced Conditioned Catalepsy

“…A particularly interesting case in the field of Pavlovian conditioning using drugs as USs is conditioning produced by pairing a neutral stimulus (typically a new experimental context) with the effects of haloperidol. This antipsychotic drug produces extrapyramidal side effects such as parkinsonism, akinesia, and acute dystonia (Lanis and Schmidt, 2001;Oliveira et al, 2016) that are related to a decrease in dopamine transmission in the striatal areas caused by the blockade of D2 receptors (Klemm, 1989;Dias et al, 2012;Barroca et al, 2019). The complexity of the conditioning process using haloperidol as the US is shown in experiments in which opposing results appear depending on the dose of the drug and type of test used.…”