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

Abstract

RationaleThe 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.ObjectiveThe 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.ResultsSCOP 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.ConclusionMuscarinic m1 antagonists should be considered an interesting alternative for SCOP as a pharmacological model for cholinergic mnemonic deficits in animals.

Modelling Alzheimer-like cognitive deficits in rats using biperiden as putative cognition impairer

“…As a result, the use of BIP is expected to induce cognitive deficits such as impaired learning and memory without serious peripheral effects [9]. Klinkenberg and Blokland [7] confirmed these expectations in rats.…”

“…Scopolamine, a non-selective muscarinic antagonist, has become the gold standard for inducing AD-like cognitive deficits pharmacologically [1,2]. This compound, however, may induce many peripheral effects (see [2,7,8]) which can bias the results [2,7]. It has been suggested that the anticholinergic drug biperiden (BIP) represents an alternative.…”

“…It has been suggested that the anticholinergic drug biperiden (BIP) represents an alternative. BIP effectively induced cognitive deficits in various species, including humans [7], is approved for human use as antiparkinsonian agent and appears to be tolerated at high doses without eliciting serious signs of toxicity. More importantly, BIP is a selective M1-antagonist [9,10].…”

123I-Iododexetimide Preferentially Binds to the Muscarinic Receptor Subtype M1 In Vivo

“…Pharmacologic imaging studies, electrophysiologic studies, and behavioral animal studies further support a role for M 1 Rs in learning and memory (14)(15)(16). In this regard, recently developed drugs selectively targeting M 1 R, including M 1 agonists and positive allosteric modulators, have helped to further define the role of this receptor subtype in cognition (5,(8)(9)(10), providing further impetus for clinical development of therapies for diseases associated with cognitive deficits.…”

Effects of Rhodiola rosea extract on passive avoidance tests in rats

“…The scopolamine model is used extensively for preclinical testing of new substances designed to treat cognitive impairment [9].…”