ArticlePsychopharmacology2005
Comparison of the effects of clozapine and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on progressive ratio schedule performance: evidence against the involvement of 5-HT1A receptors in the behavioural effects of clozapine.
Article in Psychopharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- Quantitative analysis of performance on a progressive-ratio schedule: effects of reinforcer type, food deprivation and acute treatment with Δ⁹-tetrahydrocannabinol (THC).Behavioural processes · 2015Article
- Phenylpiperazine derivatives with selectivity for dopamine D3 receptors modulate cocaine self-administration in rats.Neuropharmacology · 2012Article
- A theory of behaviour on progressive ratio schedules, with applications in behavioural pharmacology.Psychopharmacology · 2012Review
- Modeling operant behavior in the Parkinsonian rat.Behavioural brain research · 2009Article
- Effect of reinforcer magnitude on performance maintained by progressive-ratio schedules.Journal of the experimental analysis of behavior · 2009Article
- Progressive ratio schedules of reinforcement.Journal of experimental psychology. Animal behavior processes · 2009Article
- Effect of quinolinic acid-induced lesions of the subthalamic nucleus on performance on a progressive-ratio schedule of reinforcement: a quantitative analysis.Behavioural brain research · 2008Article
- Effect of quinolinic acid-induced lesions of the nucleus accumbens core on performance on a progressive ratio schedule of reinforcement: implications for inter-temporal choice.Psychopharmacology · 2008Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
rationalePerformance on progressive ratio schedules has been proposed as a means of assessing the effects of drugs on the efficacy of reinforcers. A mathematical model (Killeen PR (1994) Mathematical principles of reinforcement. Behav Brain Sci 17:105-172) affords a basis for quantifying the effects of drugs on progressive ratio schedule performance. The model postulates a bitonic function relating response rate and ratio size. One parameter of the function, a, expresses the motivational effect of the reinforcer, whereas another parameter, delta, expresses the minimum time needed to execute a response, and is regarded as an index of 'motor capacity'. Previously we found that the atypical antipsychotic clozapine increased a, indicating an increase in reinforcer efficacy; a similar effect was observed with the 5-hydroxytryptamine (5-HT)(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). It has been suggested that some of clozapine's behavioural effects are mediated by agonistic action at 5-HT(1A) receptors.
objectiveThis study was conducted to compare the effects of clozapine and 8-OH-DPAT on progressive ratio schedule performance.
methodsRats were trained under a time-constrained progressive ratio schedule (50-min sessions). In experiment 1, they received acute doses of clozapine (4 mg kg(-1)) and 8-OH-DPAT (100 microg kg(-1)), alone and in combination with the 5-HT(1A) receptor antagonist N-[2-(4-[2-methoxyphenyl]-1-piperazinyl)ethyl]-N-2-yridinylcyclohexanecarboxamide (WAY-100635; 30 microg kg(-1)). In experiment 2, the effects of clozapine (2, 4 and 8 mg kg(-1)) and 8-OH-DPAT (25, 50 and 100 microg kg(-1)) were compared between intact rats and rats whose 5-HTergic pathways had been ablated by 5,7-dihydroxytryptamine (5,7-DHT).
resultsIn both experiments, clozapine and 8-OH-DPAT increased a and delta. In experiment 1, WAY-100635 abolished the effect of 8-OH-DPAT on a and delta, but did not alter clozapine's effects on these parameters. In experiment 2, the effects of clozapine and 8-OH-DPAT did not differ between sham-lesioned and 5,7-DHT-lesioned rats.
conclusionsThe results confirm previous findings on the effects of clozapine and 8-OH-DPAT on progressive ratio schedule performance. 8-OH-DPAT's effects are probably mediated by post-synaptic 5-HT(1A) receptors; clozapine's effects are mediated by a different mechanism, which does not appear to involve 5-HT(1A) receptors and which does not depend upon an intact 5-HTergic pathway.
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