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.
Cocaine addiction is a severe psychiatric condition for which currently no effective pharmacotherapy is available. Brain mechanisms for the establishment of addiction‐related behaviors are still not fully understood, and specific biomarkers for cocaine use are not available. Sphingolipids are major membrane lipids, which shape neuronal membrane composition and dynamics in the brain. Here, we investigated how chronic cocaine exposure during establishment of addiction‐related behaviors affects the activity of the sphingolipid rheostat controlling enzymes in the brain of rats. As we detected specific effects on several enzymes in the brain, we tested whether the activity of selected enzymes in the blood may serve as potential biomarker for cocaine exposure in non‐human primates (Callithrix penicillata). We found that intravenous cocaine self‐administration led to a reduced mRNA expression of Cers1, Degs1 and Degs2, and Smpd1 in the prefrontal cortex of rats, as well as a reduction of Cers4 expression in the striatum. These effects reversed after 10 days of abstinence. Monkeys showed a robust cocaine‐induced place preference (CPP). This coincided with a reduction in blood acid sphingomyelinase (ASM) activity after CPP establishment. This effect normalized after 15 days of abstinence. Altogether, these findings suggest that the establishment of cocaine addiction‐related behaviors coincides with changes in the activity of sphingolipid controlling enzymes. In particular, blood ASM levels may serve as a translational biomarker for recent cocaine exposure.
Methylphenidate (MPH) is a central nervous system stimulant used as a pharmacotherapy to treat Attention-Deficit/Hyperactivity Disorder and narcolepsy. Scientists are concerned that MPH use could lead to increase the risk of vulnerability to drug abuse later in life. Little work has been carried out on the addictive potential of MPH in non-human primates (NHP). In the present study we intend to evaluate whether the MPH is able to produce a conditioned response and if the exposure to cannabidiol (CBD) during the extinction trial of the conditioned preference place (CPP) paradigm can inhibit the reinstatement of the response in male marmoset monkeys. Animals received alternating intraperitoneal (i.p.) injections of either MPH (5mg/kg) or saline (SAL) to a daily 15 min conditioning trial during 10 consecutive days in drug -and saline-paired compartments, respectively, of a CPP box. After a place preference test the animals were submitted to daily CBD injection in a 15min extinction trial, until the association b etween MPH and the MPH-paired compartment was extinguished. Then, 24h after the last extinction trial, animals received a priming dose of MPH (1mg/kg) and were submitted to a 15min retest trial. We found that MPH induced strong and long -lasting reinforcing properties during the conditioning period even after extinction training and reinstatement test. Therefore, MPH induced a CPP response in a NHP model and CBD administration could not inhibit the reinstatement of the MPH-induced CPP response.
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