Effects of clozapine and haloperidol on baseline levels of vacuous jaw movements in aged rats
Introduction
Clozapine has been effective in treating schizophrenics and schizophrenics who have been resistant to classical neuroleptics, without a high incidence of extrapyramidal side effects 12, 18, 20, 27, 35, 63. The long-term effects of clozapine have been reported to be superior to those observed with typical neuroleptic drugs 36, 39, 50. Furthermore, clozapine does not appear to produce tardive dyskinesia 10, 37and appears to be an effective treatment for tardive dyskinesia that is unresponsive to other remedial forms of treatment 21, 38, 46. Clozapine is believed to have stronger effects on the mesocorticolimbic dopamine system, rather than the nigrostriatal system 2, 5, 6, 8, 33and this property is believed to he essential for blocking psychosis without producing extrapyramidal side effects [1].
Classic antipsychotic drugs produce a syndrome of vacuous jaw movements in rats, which is characterized by a rapid opening and closing of the jaw which is not directed at any particular stimulus 13, 23, 29, 30, 57, 58, 59, 67, 69. The effects of antipsychotic drugs in aged rats has important implications for human functioning, given that there is an increased incidence of extrapyramidal side effects with classic neuroleptic administration to elderly humans 3, 15, 34and these symptoms sometimes remain after discontinuation of drug [66]. These increases may reflect changes in catecholamine functioning that are age-related in humans [51], such as cell loss of neurons in the putamen [7]. Similar changes in dopaminergia functioning have been found in rats 16, 25, 33, 64, 71. For example, age-related impairments in catecholamine functioning have been established at the pre- and post-synaptic levels in the basal ganglia and hypothalamus of rats and primates 17, 43. Several studies have indicated that spontaneous non-drug induced vacuous jaw movements in rats increase with age 26, 31, 60, 69, 73, 74, and these vacuous jaw movements have been linked to striatal dopamine functioning [30].
Clozapine has reportedly been given to individuals of all ages 45, 50, but there is only a single case study in the literature supporting the use of clozapine in the treatment of the elderly [4]. Acute administration of clozapine does not elevate vacuous jaw movements in young rats 26, 31or produce dystonias in adult monkeys [11]. The administration of clozapine for 12 months to young adult rats does produce elevations in vacuous jaw movements [58]. However, the effects of acute administration of clozapine to aged rats has not yet been explored. The purpose of the present set of experiments is to determine the impact of clozapine and haloperidol on vacuous jaw movements in a group of aged rats. The doses selected for repeated administration in the present study were selected because of their ability to partially reverse psychotomimetic-induced social withdrawal [68]and from parallel findings with these doses in young rats [67].
Section snippets
Subjects
The subjects in this experiment were 36 male Sprague-Dawley rats obtained from Harlan Sprague–Dawley (Indianapolis, IN). The rats were between 20 and 24 months of age at the start of the study and weighed between 500 and 650 g. All rats were housed individually in a colony room maintained at 20°C, with a 12-h light/dark cycle (lights on at 07:00 h). Standard lab chow and water were available ad libitum.
Drugs
Haloperidol was obtained from Sigma (St. Louis, MO) and injected in doses of either 0.04,
Results
Interrater reliabilities for the two observers were calculated using the Pearson r on each day of the study. The two observers achieved an interrater reliability of 0.88 or better on all 4 observation days. Therefore, all data analysis was performed on the arithmetic mean of the observer's vacuous jaw movement tallies.
The effect of each drug on vacuous jaw movements was analyzed separately using a mixed three by four ANOVA, with repeated measures across days. The results of the effect of
Discussion
The results of the present study indicated that 0.4 mg/kg of haloperidol elevated vacuous jaw movements in aged rats after the first administration and these elevations became more pronounced with repeated administration. The 0.1 mg/kg of haloperidol elevated vacuous jaw movements in this population with repeated administration. The findings regarding haloperidol are consistent with the literature on perioral movements in rats [69]and monkeys [22]. While clozapine does not elevate vacuous jaw
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