Effects of chronic haloperidol and clozapine on vacuous chewing and dopamine-mediated jaw movements in rats: evaluation of a revised animal model of tardive dyskinesia

Abstract

Rats received haloperidol (1.0 mg/kg i.p.) or clozapine (10 mg/kg i.p.), twice daily for 4 weeks: vacuous chewing--recorded 26 h after the final injection--similarly increased in both groups. Three h later, the rats were challenged with dopaminomimetics, and automatically recorded jaw movements were analysed. Both apomorphine and a mixture of D1 and D2 receptor agonists (SKF 38393 resp. quinpirole) increased jaw movements in haloperidol-treated, but not clozapine-treated rats; SKF 38393 or quinpirole remained ineffective, when given alone. A fixed dose of quinpirole together with increasing doses of SKF 38393, but not a fixed dose of SKF 38393 together with increasing doses of quinpirole, produced a dose-dependent increase in jaw movements in otherwise non-treated rats, suggesting that the noted haloperidol-induced increase was due to a shift in the D1-D2 receptor balance towards a predominance of D1 receptors. This study presents a new animal model of tardive dyskinesia with predictive validity, good reliability and, especially, great efficiency.

Multidose Risperidone Treatment Evaluated in a Rodent Model of Tardive Dyskinesia

“…Moreover, the movement quality in these animals was jerky and irregular, not a regular tremor. We and others (Gunne et al, 1982;Ikeda et al, 1999;Tamminga et al, 1990;Trevitt et al, 1999) have argued for a connection between these VCMs and TD, and have suggested and tested a systems pathophysiology distinct from parkinsonism to account for the movements (Shirakawa and Tamminga, 1994;Sakai et al, 2001).…”

Adenosine A_2A-Receptor Antagonism and Pathophysiology of Parkinson’s Disease and Drug-Induced Movement Disorders

“…In this theory, dyskinesia results from an imbalance between D 2 - and D 1 -receptor function, with a shift toward a predominance of D 1 receptors. This shift has been linked to a dose-dependent increase in drug-induced jaw movement in rats [38]. …”

Behavioral responses to methylphenidate and apomorphine in rats exposed neonatally to bisphenol-A

“…We have previously reported that jaw movements occurring in response to stimulation of dopamine receptors is a convenient parameter for examination of dopamine receptor function (15)(16)(17)(18). On the basis of these findings, we hypothesized that the function of postsynaptic dopamine receptors in the brain structures that are involved in the elicitation of jaw movements would be enhanced in bisphenol-A-pretreated rats relative to vehicle-pretreated rats at around 8 weeks of age.…”

“…During light phase observations, the number of episodes of other types of behavior, i.e. rearing, sniffing and grooming, was also counted visually by a trained observer who was blind to the treatments (15,(19)(20)(21)(22): each number (rearing) or episode (sniffing or grooming) was scored as a "1". Rearing is characterized by rats standing up (including use of the cage wall) on the two hindlimbs.…”