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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 (0.1, 0.3 mg/kg, IP) and BIP (3, 10 mg/kg, IP) on performance measures in the attention task. a, b Percentage correct responses. SCOP decreased accuracy independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on accuracy. c, d Percentage omissions. SCOP increased response omissions independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on response omissions. e, f Response time. SCOP slowed sensorimotor responding at a dose of 0.3 mg/kg. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (**P <0.01; ***P <0.001)
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Fig3: The effects of SCOP (0.1, 0.3 mg/kg, IP) and BIP (3, 10 mg/kg, IP) on performance measures in the attention task. a, b Percentage correct responses. SCOP decreased accuracy independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on accuracy. c, d Percentage omissions. SCOP increased response omissions independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on response omissions. e, f Response time. SCOP slowed sensorimotor responding at a dose of 0.3 mg/kg. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (**P <0.01; ***P <0.001)

Mentions: Figure 3a, b shows the effects of SCOP and BIP on percentage correct in the attention task. In the mixed model ANOVA, the within-subject effect of dose on percentage correct did not vary per level of drug and stimulus duration (no dose × drug × stimulus duration interaction effect; F(4, 68) = 0.75, n.s.). However, the within-subject effect of dose on percentage correct did vary per level of drug (dose × drug interaction effect; F(2, 34) = 7.96; P < 0.01). The within-subject effect of stimulus duration on percentage correct was also different per level of drug (stimulus duration × drug interaction effect; F(2, 34) = 3.82; P < 0.05). Therefore separate repeated measures ANOVAs for the two levels of drug were performed. In the group treated with SCOP, the within-subject effect of stimulus duration on percentage correct was not different per level of dose (no stimulus duration × dose interaction effect; F(4, 36) = 0.83, n.s.; see Fig. 3a). There was a reduction in percentage correct responses with shorter stimulus durations (main effect of stimulus duration; F(2, 18) = 40.06; P < 0.001). SCOP decreased percentage correct responses in the attention task (main effect of dose; F(2, 18) = 20.55; P < 0.001). Post hoc analysis showed that at a dose of 0.3 mg/kg SCOP lowered percentage correct score as compared with the vehicle condition (P < 0.01). In the group treated with BIP, the within-subject effect of stimulus duration on percentage correct was not different per level of dose (no stimulus duration × dose interaction effect; F(4, 32) = 0.36, n.s.; see Fig. 3b). Moreover, shorter stimulus durations reduced percentage correct (main effect of stimulus duration; F(2, 16) = 149.29; P < 0.001). BIP treatment did not affect the measure percentage correct (no main effect of dose; F(2, 16) = 2.69, n.s.).Fig. 3


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 (0.1, 0.3 mg/kg, IP) and BIP (3, 10 mg/kg, IP) on performance measures in the attention task. a, b Percentage correct responses. SCOP decreased accuracy independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on accuracy. c, d Percentage omissions. SCOP increased response omissions independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on response omissions. e, f Response time. SCOP slowed sensorimotor responding at a dose of 0.3 mg/kg. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (**P <0.01; ***P <0.001)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3090581&req=5

Fig3: The effects of SCOP (0.1, 0.3 mg/kg, IP) and BIP (3, 10 mg/kg, IP) on performance measures in the attention task. a, b Percentage correct responses. SCOP decreased accuracy independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on accuracy. c, d Percentage omissions. SCOP increased response omissions independent of stimulus duration at a dose of 0.3 mg/kg. BIP did not have an effect on response omissions. e, f Response time. SCOP slowed sensorimotor responding at a dose of 0.3 mg/kg. BIP did not have an effect on sensorimotor responding. Data represent mean (+SEM). Asterisks indicate differences from vehicle condition (**P <0.01; ***P <0.001)
Mentions: Figure 3a, b shows the effects of SCOP and BIP on percentage correct in the attention task. In the mixed model ANOVA, the within-subject effect of dose on percentage correct did not vary per level of drug and stimulus duration (no dose × drug × stimulus duration interaction effect; F(4, 68) = 0.75, n.s.). However, the within-subject effect of dose on percentage correct did vary per level of drug (dose × drug interaction effect; F(2, 34) = 7.96; P < 0.01). The within-subject effect of stimulus duration on percentage correct was also different per level of drug (stimulus duration × drug interaction effect; F(2, 34) = 3.82; P < 0.05). Therefore separate repeated measures ANOVAs for the two levels of drug were performed. In the group treated with SCOP, the within-subject effect of stimulus duration on percentage correct was not different per level of dose (no stimulus duration × dose interaction effect; F(4, 36) = 0.83, n.s.; see Fig. 3a). There was a reduction in percentage correct responses with shorter stimulus durations (main effect of stimulus duration; F(2, 18) = 40.06; P < 0.001). SCOP decreased percentage correct responses in the attention task (main effect of dose; F(2, 18) = 20.55; P < 0.001). Post hoc analysis showed that at a dose of 0.3 mg/kg SCOP lowered percentage correct score as compared with the vehicle condition (P < 0.01). In the group treated with BIP, the within-subject effect of stimulus duration on percentage correct was not different per level of dose (no stimulus duration × dose interaction effect; F(4, 32) = 0.36, n.s.; see Fig. 3b). Moreover, shorter stimulus durations reduced percentage correct (main effect of stimulus duration; F(2, 16) = 149.29; P < 0.001). BIP treatment did not affect the measure percentage correct (no main effect of dose; F(2, 16) = 2.69, n.s.).Fig. 3

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