Effect of age on behavioral responses and tissue levels of apomorphine in the rat

Campbell, Andrea Louise; Baldessarini, Ross J.; Stoll, Andrew L.; Teicher, Martin H.; Maynard, P.

doi:10.1016/0028-3908(84)90103-5

Cited by 26 publications

(6 citation statements)

References 26 publications

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“…Significant differences from vehicle-treated animals: **P < 0.01; * P < 0.05. Increased stereotypy responses to apomorphine in aged rodents appear to have a basis in higher drug concentrations in plasma and brain (Watanabe et al, 1982;Campbell et al, 1984). In male Sprague-Dawley rats, as used here, there is a lack of parallelism between changes in body weight and in response to or tissue level of apomorphine (for detailed analysis, see Campbell et al, 1984); thus, the greater body weight of aged animals does not appear to account for the altered response to a drug given on a mgkg-I basis.…”

Section: Discussionmentioning

confidence: 99%

“…While overall stereotypy responses to the classical agonist apomorphine are enhanced with aging (Smith et al, 1978;Randall et al, 1981), recent data indicate a prominent influence of altered pharmacokinetics, such that higher plasma and brain levels of apomorphine are evident in aged animals (Watanabe et al, 1982;Campbell et al, 1984). Additionally, apomorphine is a non-selective agonist at both D1-and D2-receptors (Kebabian & Calne, 1979;Seeman, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Behavioural responses to the selective D₁‐dopamine receptor agonist R‐SK&F 38393 and the selective D₂‐agonist RU 24213 in young compared with aged rats

Molloy

Waddington

1988

British J Pharmacology

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1 In aged male Sprague-Dawley rats (22 months) with a selective loss of D2-but not of DI-dopamine receptors, stereotyped behaviour induced by 0.5mg kg-apomorphine was increased and prolonged in comparison with young (4 month) counterparts. This suggested a pharmacokinetic effect rather than a pharmacodynamic change. 5 It is suggested that age-related decline in D2-receptor activity may have greater functional consequences in relation to D-0:D2-interactions than in simply influencing responsivity to a D2-agonist. Such interactive effects should be taken into account when considering the pathophysiology and treatment of age-related extrapyramidal movement disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Behavioural responses to the selective D₁‐dopamine receptor agonist R‐SK&F 38393 and the selective D₂‐agonist RU 24213 in young compared with aged rats

Molloy

Waddington

1988

British J Pharmacology

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“…There are also complex changes in sensitivity to dopamine agonists between young and mature rats. These include moderately increasing sensitivity to behavioral arousal by agonists that, in part, reflects losses in efficiency of drug metabolism that also occur in humans (Campbell et al 1984) as well as diminishing potency of dopamine agonists at autoreceptors that modulate the production and release of dopamine in the developing rat brain (Andersen and Gazzara 1995). Moreover, physiologic mechanisms for adjusting to the actions of neuroleptics on cerebral dopamine systems become more effective with maturation, for example, resulting in less steep (evidently "less brittle" or better modulated) increases of dopamine turnover by doses of a neuroleptic in the maturing postnatal rat brain (Teicher et al 1993).…”

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confidence: 98%

Dosing of Antipsychotic Agents in Pediatric Populations

Baldessarini¹,

Teicher²

1995

Journal of Child and Adolescent Psychopharmacology

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In this issue, Mandoki (1995) and Simeon and his colleagues (1995) report on clinical experiences with the recently introduced antipsychotic agent, risperidone, in a total of 17 severely disturbed children and adolescents. Studies of this novel drug in young patients are still rare, and these two reports raise several timely questions that are both theoretically and clinically significant. They contribute to the still limited testing of dose-response relationships of the older neuroleptic agents in pédiatrie populations ). Risperidone is of special interest because it is hoped to be better tolerated, if not more effective, than standard neuroleptics. Its direct comparison with the standard atypical antipsychotic agent, clozapine, suggests that risperidone may be similar in antipsychotic efficacy and possibly better tolerated (Kleiser et al. 1995). Critical comparison studies are required to test this possibility, particularly in pédiatrie populations. Among potential disadvantages of risperidone for pédiatrie application are the relatively large minimum dosage form (1.0 mg scored tablets) and the recommendation of twice-daily administration despite a mean half-life of risperidone and its active 9-hydroxy metabolite of about 20 hours (Kane 1994, Janssen 1995. In addition, risperidone is relatively expensive, costing about $6-10 daily. Mandoki (1995) suggests that pédiatrie patients may tolerate risperidone less well than adults and so require lower absolute as well as mg/kg doses, based on observing high rates of adverse effects in pédiatrie patients given daily doses of risperidone of 2-6 mg. Children and adolescents are reported to be at higher risk than young and middle-aged adults for certain extrapyramidal side effects (EPS) induced by standard neuroleptic agents-particularly parkinsonian bradykinesia and acute dystonia (Keepers et al. 1983). These findings are also in accord with the results of observations in laboratory animals, in which the behavioral or neurochemical potency of various neuroleptic agents declined (rising ED50) by as much as 75-fold between neonatal and adult ages in the laboratory rat, with a later increase in senescence Baldessarini 1981, Teicher et al. 1993). Similar maturational changes were found when chemically dissimilar neuroleptics were administered intracerebrally in order to avoid possible developmental changes in drug disposition or metabolism (Campbell et al. 1988).The high sensitivity to antipsychotic agents in immature laboratory animals runs counter to clinical evidence that children are protected by more efficient metabolic clearance of psychotropic agents than adults (Morselli 1977, Wilens et al. 1992. Therefore, powerful developmental changes in brain function contributing to altered pharmacodynamics of antipsychotic agents probably underlie a maturational decrease in sensitivity to neuroleptics (Teicher and Baldessarini 1987). Relevant changes in the maturing rat forebrain include a rising postnatal abundance of dopamine receptors into adolescence, with some decrease...

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“…At the end of the three replications, the mean time spent by the rat without moving was calculated for each test. This technique was selected over the other alternative methods due to the fact that previous studies demonstrated its high sensitivity to neuroleptics (Campbell et al 1984). The catalepsy scores were obtained each day at 3, 6 and 12 hr after drug administration.…”

Section: Methodsmentioning

confidence: 99%

“…Different methods used to induce undernutrition change maternal behaviour and other non-nutritional variables in distinct ways (Crnic 1980;Fleischer & Turkewitz 1981;Frankova 1973;Galler & Kanis 1987;Galler & Turkewitz 1977;Lynch 1976;Rocha et al 1988;Smart 1983;Wiener et al 1978), which may influence the behavioural response to drugs. Catalepsy and locomotion, two classes of behavior that are presumably controlled by different pathways of the dopaminergic system (Beninger 1983;Campbell et a/. 1984;Fink & Smith 1980;Museo &Wise 1990) were investigated.…”

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confidence: 99%

Undernutrition During Suckling Changes the Sensitivity to Haloperidol and Chlorpromazine in Two Behavioural Measures in Weaning Rats

Rocha

Santos

Rocha

et al. 1997

Pharmacology & Toxicology

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Undernutrition during critical periods of development may cause changes in the behavioural responses of rats to centrally acting drugs. In the present study, the effects of undernutrition during suckling on the behavioural responses of 21-days-old rats to chlorpromazine (0, 2.5, 5, 10 and 20 mg/kg) or haloperidol (0, 0.125, 0.25, 0.5, I or 2 mg/kg) were examined. Locomotion was assessed at 1 hr 30 rnin., 4 hr 30 min., 7 hr 30 min. and 10 hr 30 rnin., and catalepsy was scored at 3 hr, 6 hr and 9 hr after drug administration. Drug was injected on two consecutive days. On day 1, salinetreated undernourished rats showed significantly greater locomotion activity than did normal rats. The neuroleptic-induced inhibition of locomotor activity in undernourished rats was significantly less than that observed in normal rats from 4 hr 30 min. to 10 hr 30 min. (chlorpromazine) or from 7 hr 30 min. to 10 hr 30 min. (haloperidol). On day 2, a similar trend was observed but only in rats injected with 5 mg/kg chlorpromazine or 0.5, 1, and 2 mg/kg haloperidol. On day 1, the catalepsy scores at 3 hr revealed no significant difference between nutritional groups, but at 6 hr undernourished rats responded significantly less to chlorpromazine or haloperidol. On day 2, undernourished rats were less responsive to neuroleptics than normal rats, but the effect was not so evident as observed on day 1. The present results suggest that the behavioural effects of chlorpromazine and haloperidol are less persistent in undernourished rats, possibly due to differences in drug distribution and elimination, when compared to well-nourished rats.

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Effect of age on behavioral responses and tissue levels of apomorphine in the rat

Cited by 26 publications

References 26 publications

Behavioural responses to the selective D₁‐dopamine receptor agonist R‐SK&F 38393 and the selective D₂‐agonist RU 24213 in young compared with aged rats

Behavioural responses to the selective D₁‐dopamine receptor agonist R‐SK&F 38393 and the selective D₂‐agonist RU 24213 in young compared with aged rats

Dosing of Antipsychotic Agents in Pediatric Populations

Undernutrition During Suckling Changes the Sensitivity to Haloperidol and Chlorpromazine in Two Behavioural Measures in Weaning Rats

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Effect of age on behavioral responses and tissue levels of apomorphine in the rat

Cited by 26 publications

References 26 publications

Behavioural responses to the selective D1‐dopamine receptor agonist R‐SK&F 38393 and the selective D2‐agonist RU 24213 in young compared with aged rats

Behavioural responses to the selective D1‐dopamine receptor agonist R‐SK&F 38393 and the selective D2‐agonist RU 24213 in young compared with aged rats

Dosing of Antipsychotic Agents in Pediatric Populations

Undernutrition During Suckling Changes the Sensitivity to Haloperidol and Chlorpromazine in Two Behavioural Measures in Weaning Rats

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Product

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Behavioural responses to the selective D₁‐dopamine receptor agonist R‐SK&F 38393 and the selective D₂‐agonist RU 24213 in young compared with aged rats

Behavioural responses to the selective D₁‐dopamine receptor agonist R‐SK&F 38393 and the selective D₂‐agonist RU 24213 in young compared with aged rats