Scopolamine Induces Deficits in Spontaneous Object-Location Recognition and Fear-Learning in Marmoset Monkeys

Abstract

The non-selective muscarinic receptor antagonist scopolamine (SCP) induces memory deficits in both animals and humans. However, few studies have assessed the effects of amnesic agents on memory functions of marmosets – a small-bodied neotropical primate that is becoming increasingly used as a translational model for several neuropathologies. Here we assessed the effects of an acute SCP administration (0.03 mg/kg, sc) on the behavior of adult marmoset monkeys in two tasks. In the spontaneous object-location (SOL) recognition task, two identical neutral stimuli were explored on the sample trial, after which preferential exploration of the displaced versus the stationary object was analyzed on the test trial. In the fear-motivated behavior (FMB) procedure, the same subjects were submitted to an initial baseline trial, followed by an exposure period to a snake model and lastly a post-exposure trial. All trials and inter-trial intervals lasted 10 min for both tests. Results showed that on the SOL test trial, the saline group explored the displaced object significantly longer than its identical stationary counterpart, whereas SCP-treated marmosets explored both objects equivalently. In the FMB test, the saline group – but not the SCP-treated animals – spent significantly less time where the stimulus had been specifically encountered and more time being vigilant of their surroundings, compared to pre-exposure levels. Drug-related effects on general activity, overall exploration (SOL task) and behavioral response to the aversive stimulus (FMB task) were not observed. SCP thus impaired the marmosets’ short-term ability to detect changes associated with the spatial location of ethologically irrelevant (SOL task) and relevant stimuli (FMB task). Similar results have been reported in other animal species. Marmosets may thus help reduce the translational gap between pre-clinical studies and memory-associated human pathologies.

Neuropharmacological evaluation on four traditional herbs used as nervine tonic and commonly available as Shankhpushpi in India

“…It was seen that animals receiving only scopolamine on day 9 (Cook and Weidley's pole climbing apparatus) and day 14 (Morris water maze task) showed a considerable loss of memory and amnesia produced was persistent. There is substantial evidence that muscarinic receptor blockade by drugs like scopolamine results into disruptions of various tasks related to performance of memory [32], [33]. Reduction in the number of avoidance responses is an evidence of amnesia during inhibitory avoidance test conducted after administration of scopolamine.…”

Neutral ceramidase is a marker for cognitive performance in rats and monkeys

“…Long-term memory was tested in marmosets using a NOR test. A white rectangular OF (130 × 75 × 40 cm) was used, as previously described [ 34 , 35 ]. It had three aluminum sides, whereas the fourth side was made of transparent glass.…”

Acetylcholine and Spontaneous Recognition Memory in Rodents and Primates

“…injection of scopolamine (which will have central effects across both regions) impairs spontaneous recognition memory, although only at higher doses than those which impaired the same animals on a radial maze spatial learning task (Ennaceur & Meliani, 1992). Barros and colleagues have recently shown object location memory deficit in marmosets as well after scopolamine was given ip, but at doses that also impaired their contextual fear-conditioning (Melamed, de Jesus, Maior, & Barros, 2017). Closer investigation shows that whilst ip scopolamine impairs spontaneous recognition, it only does so when delivered during the encoding (sample) phase, but not when administered during the retrieval (test) phase (Melamed et al, 2017;Warburton et al, 2003).…”

“…Barros and colleagues have recently shown object location memory deficit in marmosets as well after scopolamine was given ip, but at doses that also impaired their contextual fear-conditioning (Melamed, de Jesus, Maior, & Barros, 2017). Closer investigation shows that whilst ip scopolamine impairs spontaneous recognition, it only does so when delivered during the encoding (sample) phase, but not when administered during the retrieval (test) phase (Melamed et al, 2017;Warburton et al, 2003). Scopolamine-induced impairment in rat spontaneous object recognition and marmoset object discrimination can also be reversed by a number of nootropic drugs (e.g.…”

“…This separation requires the cholinergic system to promote encoding of separate locations despite high levels of spatial interference. With the use of spontaneous recognition tasks to explore cholinergic function across rodents (A Easton et al, 2011;Seel et al, 2018b;Winters & Bussey, 2005) and primates (Melamed et al, 2017) we will be able to make more reliable comparisons across species. In addition, evidence that spontaneous recognition tasks of episodic memory can be translated to episodic memory in humans (Ameen-Ali et al, 2017;Easton, Webster, et al, 2012) taking us to a position where we are now able to improve translation from animal studies to the clinic.…”