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.
Highlights
Over the years central cholinergic signaling has become increasingly implicated in different learning and memory processes (Hasselmo and Sarter, 2011)
During the initial baseline trial of the fear-motivated behavior (FMB) task, held in the absence of the snake stimulus, all marmosets spent a comparable amount of time in the four corner quadrants of the OF arena (SAL group – section 1: 72 ± 18, section 2: 77 ± 19, section 3: 71 ± 13, section 4: 80 ± 9; SCP group – section 1: 69 ± 19, section 2: 78 ± 21, section 3: 74 ± 22, section 4: 78 ± 18; mean ± SEM in seconds; quadrant effect: F3,21 = 0.09, p = 0.85; treatment effect: F1,7 = 0.01, p = 0.99; interaction: F3,21 = 0.02, p = 0.97)
After being confronted with the aversive stimulus, the SAL-treated marmosets spent significantly less time in the snake-paired quadrant of the OF apparatus compared to the levels seen prior to its exposure, whereas the SCP group spent a similar amount of time on both trials
Summary
Over the years central cholinergic signaling has become increasingly implicated in different learning and memory processes (Hasselmo and Sarter, 2011). In rodents and non-human primates (NHPs), the use of excitotoxic (e.g., rodents: Baxter and Bucci, 2013; marmosets: Ridley et al, 1986; macaques: Aigner et al, 1991a) and more specific immunotoxic lesions (e.g., rodents: Easton et al, 2011; marmosets: Ridley et al, 1999; macaques: Turchi et al, 2005) of basal forebrain cholinergic projections to the cortex disrupted several learning and memory processes When using this approach, the degree of the impairment can vary significantly according to the specificity and extent of the lesion and the type of cognitive task being assessed, with the possible involvement of non-cholinergic afferents. SCP has become a frequently used preclinical pharmacological tool to assess memory (dys)function (Klinkenberg and Blokland, 2010)
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