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A comparison of scopolamine and biperiden as a rodent model for cholinergic cognitive impairment.

Klinkenberg I, Blokland A - Psychopharmacology (Berl.) (2011)

Bottom Line: However, its use remains controversial due to the wide spectrum of behavioral effects of this drug.This was done by comparing the effects of SCOP and BIP using a battery of operant tasks: fixed ratio (FR5) and progressive ratio (PR10) schedules of reinforcement, an attention paradigm and delayed nonmatching to position task.BIP had no effect on food motivation (PR10) or attention.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands. inge.klinkenberg@maastrichtuniversity.nl

ABSTRACT

Rationale: The nonselective muscarinic antagonist scopolamine hydrobromide (SCOP) is employed as the gold standard for inducing memory impairments in healthy humans and animals. However, its use remains controversial due to the wide spectrum of behavioral effects of this drug.

Objective: The present study investigated whether biperiden (BIP), a muscarinic m1 receptor antagonist, is to be preferred over SCOP as a pharmacological model for cholinergic memory deficits in rats. This was done by comparing the effects of SCOP and BIP using a battery of operant tasks: fixed ratio (FR5) and progressive ratio (PR10) schedules of reinforcement, an attention paradigm and delayed nonmatching to position task.

Results: SCOP induced diffuse behavioral disruption, which included sensorimotor responding (FR5, 0.3 and 1 mg/kg), food motivation (PR10, 1 mg/kg), attention (0.3 mg/kg, independent of stimulus duration), and short-term memory (delayed nonmatching to position (DNMTP), 0.1 and 0.3 mg/kg, delay-dependent but also impairment at the zero second delay). BIP induced relatively more selective deficits, as it slowed sensorimotor responding (FR5, 10 mg/kg) and disrupted short-term memory (DNMTP, 3 mg/kg, delay-dependent but no impairment at the zero second delay). BIP had no effect on food motivation (PR10) or attention.

Conclusion: Muscarinic m1 antagonists should be considered an interesting alternative for SCOP as a pharmacological model for cholinergic mnemonic deficits in animals.

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Related in: MedlinePlus

The effects of SCOP (0.3 and 1 mg/kg, IP) and BIP (3 and 10 mg/kg, IP) on a PR10 schedule of reinforcement. a Breakpoint. SCOP decreased food motivation at a dose of 1 mg/kg. b Breakpoint. BIP did not have an effect on food motivation. c Inter-response time. SCOP slowed sensorimotor responding at a dose of 1 mg/kg. d Inter-response time. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (*P < 0.05)
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Fig2: The effects of SCOP (0.3 and 1 mg/kg, IP) and BIP (3 and 10 mg/kg, IP) on a PR10 schedule of reinforcement. a Breakpoint. SCOP decreased food motivation at a dose of 1 mg/kg. b Breakpoint. BIP did not have an effect on food motivation. c Inter-response time. SCOP slowed sensorimotor responding at a dose of 1 mg/kg. d Inter-response time. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (*P < 0.05)

Mentions: Figure 2 shows the effects of SCOP and BIP on breakpoint and inter-response time on a PR10 schedule of reinforcement. In the mixed model ANOVA, the within-subject effect of dose on breakpoint did not vary per level of drug (no dose × drug interaction effect; F(2, 36) = 0.77, n.s.). Furthermore, breakpoint was differentially affected by dose (main effect of dose; F(2, 36) = 5.57; P < 0.01). The between-subject analysis of drug showed that SCOP and BIP differentially affected breakpoint (main effect of drug; F(1, 18) = 5.93; P < 0.05). Therefore, two separate repeated measures ANOVAs for the different levels of drug were performed. For the group treated with SCOP, breakpoint in the PR10 task was reduced (main effect of dose; F(2, 18) = 3.91; P < 0.05; see Fig. 2a). Post hoc analysis showed an effect of the 1 mg/kg dose (P < 0.05). For the group treated with BIP, no change in breakpoint (no main effect of dose; F(2, 18) = 2.10, n.s.; see Fig. 2b) was found.Fig. 2


A comparison of scopolamine and biperiden as a rodent model for cholinergic cognitive impairment.

Klinkenberg I, Blokland A - Psychopharmacology (Berl.) (2011)

The effects of SCOP (0.3 and 1 mg/kg, IP) and BIP (3 and 10 mg/kg, IP) on a PR10 schedule of reinforcement. a Breakpoint. SCOP decreased food motivation at a dose of 1 mg/kg. b Breakpoint. BIP did not have an effect on food motivation. c Inter-response time. SCOP slowed sensorimotor responding at a dose of 1 mg/kg. d Inter-response time. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (*P < 0.05)
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3090581&req=5

Fig2: The effects of SCOP (0.3 and 1 mg/kg, IP) and BIP (3 and 10 mg/kg, IP) on a PR10 schedule of reinforcement. a Breakpoint. SCOP decreased food motivation at a dose of 1 mg/kg. b Breakpoint. BIP did not have an effect on food motivation. c Inter-response time. SCOP slowed sensorimotor responding at a dose of 1 mg/kg. d Inter-response time. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (*P < 0.05)
Mentions: Figure 2 shows the effects of SCOP and BIP on breakpoint and inter-response time on a PR10 schedule of reinforcement. In the mixed model ANOVA, the within-subject effect of dose on breakpoint did not vary per level of drug (no dose × drug interaction effect; F(2, 36) = 0.77, n.s.). Furthermore, breakpoint was differentially affected by dose (main effect of dose; F(2, 36) = 5.57; P < 0.01). The between-subject analysis of drug showed that SCOP and BIP differentially affected breakpoint (main effect of drug; F(1, 18) = 5.93; P < 0.05). Therefore, two separate repeated measures ANOVAs for the different levels of drug were performed. For the group treated with SCOP, breakpoint in the PR10 task was reduced (main effect of dose; F(2, 18) = 3.91; P < 0.05; see Fig. 2a). Post hoc analysis showed an effect of the 1 mg/kg dose (P < 0.05). For the group treated with BIP, no change in breakpoint (no main effect of dose; F(2, 18) = 2.10, n.s.; see Fig. 2b) was found.Fig. 2

Bottom Line: However, its use remains controversial due to the wide spectrum of behavioral effects of this drug.This was done by comparing the effects of SCOP and BIP using a battery of operant tasks: fixed ratio (FR5) and progressive ratio (PR10) schedules of reinforcement, an attention paradigm and delayed nonmatching to position task.BIP had no effect on food motivation (PR10) or attention.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands. inge.klinkenberg@maastrichtuniversity.nl

ABSTRACT

Rationale: The nonselective muscarinic antagonist scopolamine hydrobromide (SCOP) is employed as the gold standard for inducing memory impairments in healthy humans and animals. However, its use remains controversial due to the wide spectrum of behavioral effects of this drug.

Objective: The present study investigated whether biperiden (BIP), a muscarinic m1 receptor antagonist, is to be preferred over SCOP as a pharmacological model for cholinergic memory deficits in rats. This was done by comparing the effects of SCOP and BIP using a battery of operant tasks: fixed ratio (FR5) and progressive ratio (PR10) schedules of reinforcement, an attention paradigm and delayed nonmatching to position task.

Results: SCOP induced diffuse behavioral disruption, which included sensorimotor responding (FR5, 0.3 and 1 mg/kg), food motivation (PR10, 1 mg/kg), attention (0.3 mg/kg, independent of stimulus duration), and short-term memory (delayed nonmatching to position (DNMTP), 0.1 and 0.3 mg/kg, delay-dependent but also impairment at the zero second delay). BIP induced relatively more selective deficits, as it slowed sensorimotor responding (FR5, 10 mg/kg) and disrupted short-term memory (DNMTP, 3 mg/kg, delay-dependent but no impairment at the zero second delay). BIP had no effect on food motivation (PR10) or attention.

Conclusion: Muscarinic m1 antagonists should be considered an interesting alternative for SCOP as a pharmacological model for cholinergic mnemonic deficits in animals.

Show MeSH
Related in: MedlinePlus