Differential modulatory effects of cocaine on marmoset monkey recognition memory.

Acute and repeated exposure to cocaine alters the cognitive performance of humans and animals. How each administration schedule affects the same memory task has yet to be properly established in nonhuman primates. Therefore, we assessed the performance of marmoset monkeys in a spontaneous object-location (SOL) recognition memory task after acute and repeated exposure to cocaine (COC; 5mg/kg, ip). Two identical neutral stimuli were explored on the 10-min sample trial, after which preferential exploration of the displaced vs the stationary object was analyzed on the 10-min test trial. For the acute treatment, cocaine was given immediately after the sample presentation, and spatial recognition was then tested after a 24-h interval. For the repeated exposure schedule, daily cocaine injections were given on 7 consecutive days. After a 7-day drug-free period, the SOL task was carried out with a 10-min intertrial interval. When given acutely postsample, COC improved the marmosets' recognition memory, whereas it had a detrimental effect after the repeated exposure. Thus, depending on the administration schedule, COC exerted opposing effects on the marmosets' ability to recognize spatial changes. This agrees with recent studies in rodents and the recognition impairment seen in human addicts. Further studies related to the effects of cocaine's acute×prior drug history on the same cognitive domain are warranted.

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

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.

Sensitization of hypervigilance effects of cocaine can be induced by NK3 receptor activation in marmoset monkeys.

BACKGROUND: Cocaine is a widely abused drug which can result in the establishment of addiction. The neurokinin3-receptor (NK3-R) has been linked to cocaine addiction by genetic, epigenetic, and pharmacological studies suggesting that a cocaine-induced increase in NK3-R signaling may contribute to the establishment of cocaine addiction-related behaviors. METHODS: Here we measured cocaine-induced sensitization of vigilance- and locomotor behaviors in marmoset monkeys (Callithrix penicillata) in an open field. RESULTS: We found a sensitization of vigilance-related, but not locomotor behaviors after repeated cocaine (7mg/kg, i.p.) treatment. There was a cross-sensitization for scan frequency, but not of glance frequency, both vigilance-related behaviors, after repeated treatment with the NK3-R agonist senktide (0.2mg/kg, i.p.) given for 7 days, after a cocaine challenge (5mg/kg, i.p.). CONCLUSIONS: These data suggest that in marmoset monkeys, repeated cocaine treatment leads to a sensitization of vigilance-related behaviors, which have a prominent role in spontaneously expressed activities in this species, but not of locomotor activity. Repeated activation of NK3-Rs can mimic some of the behavioral sensitization effect and may thus contribute to the establishment of cocaine related behaviors.