Examining the effects of psychoactive drugs on complex behavioral processes in laboratory animals

Kangas, Brian D.

doi:10.1016/bs.apha.2021.09.001

Cited by 5 publications

(3 citation statements)

References 161 publications

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“…As mentioned previously, past research from our lab has demonstrated that chronic cocaine self-administration disrupted the acquisition of the SD and SDR tasks and resulted in more errors during the ED task [13,20]. It is important to note that in both of these studies, the monkeys had significantly higher cocaine intakes (mean intakes of 753.79 mg/kg and 1291.98 mg/ kg, respectively) when compared to the current study (mean intakes of 157.30 mg/kg, Table 1), suggesting that a broader range of cognitive tasks would be disrupted in the present group of monkeys, as their cocaine intakes increase [11,17]. In another study, rhesus monkeys exposed to 3.0 mg/kg of cocaine 4 days a week for 9 months showed deficits in their ability to successfully complete a version of the SDR task but not the SD task when compared to control monkeys [45].…”

Section: Cocaine Intakes and Sdr Task Performancementioning

confidence: 44%

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Cognitive performance as a behavioral phenotype associated with cocaine self-administration in female and male socially housed monkeys

Allen,

Costa,

Johnson

et al. 2024

Neuropsychopharmacol.

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Considerable research has suggested that certain cognitive domains may contribute to cocaine misuse. However, there are gaps in the literature regarding whether cognitive performance before drug exposure predicts susceptibility to cocaine self-administration and how cognitive performance relates to future cocaine intake. Thus, the present study aimed to examine cognitive performance, as measured using automated CANTAB cognitive battery, prior to and following acquisition of cocaine self-administration under a concurrent drug vs. food choice procedure in female and male socially housed cynomolgus macaques. The cognitive battery consisted of measures of associative learning (stimulus and compound discrimination tasks), behavioral flexibility (intradimensional and extradimensional tasks), and behavioral inhibition (stimulus discrimination reversal, SDR, and extra-dimensional reversal tasks). After assessing cognitive performance, monkeys were trained to self-administer cocaine (saline, 0.01–0.1 mg/kg/injection) under a concurrent cocaine vs. food schedule of reinforcement. After a history of cocaine self-administration across 3-4 years, the cognitive battery was re-assessed and compared with sensitivity to cocaine reinforcement. Results showed drug-naïve monkeys that were less accurate on the SDR task, measuring behavioral inhibition, were more sensitive to cocaine reinforcement under the concurrent cocaine vs. food choice procedure. Furthermore, following chronic cocaine self-administration, cocaine intake was a negative predictor of accuracy on the SDR behavioral inhibition task. After cocaine maintenance, monkeys with higher cocaine intakes required more trials to complete the SDR behavioral inhibition task and made more incorrect responses during these trials. No sex or social rank differences were noted. Overall, these findings suggest that cognitive performance may influence vulnerability to cocaine misuse. Also, chronic cocaine may decrease levels of behavioral inhibition as measured via the SDR task in both females and males.

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Section: Cocaine Intakes and Sdr Task Performancementioning

confidence: 44%

“…Considerable research has suggested that cognitive abilities play a crucial role in substance misuse [10][11][12]. However, it remains unclear if changes in cognitive performance occur due to chronic cocaine exposure or if cognitive differences precede cocaine exposure [13].…”

Section: Introductionmentioning

confidence: 99%

Cognitive performance as a behavioral phenotype associated with cocaine self-administration in female and male socially housed monkeys

Allen,

Costa,

Johnson

et al. 2024

Neuropsychopharmacol.

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“…For these reasons, group-housed monkeys with varied ethanol drinking histories more accurately reflect variation in human subjects. Cognitive flexibility, which involves changing one's behavior to achieve new goals and as such is critical to AUD treatment (Bates et al, 2002;Le Berre et al, 2017), can be probed in NHPs with an SDR task that has been reverse-translated from those validated in humans (Jentsch & Taylor, 1999;Weed et al, 1999;Kangas, 2022). Scopolamine, a non-selective mAChR antagonist, has been used to pharmacologically induce a cognitive deficit; the ability of drugs to reverse a scopolamine-induced deficit can be used as a measure of pro-cognitive efficacy (Klinkenberg & Blokland, 2010;Buccafusco et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Cognitive-Enhancing Effects of Acetylcholine Receptor Agonists in Group-Housed Cynomolgus Monkeys Who Drink Ethanol

Galbo-Thomma,

Epperly,

Blough

et al. 2023

J Pharmacol Exp Ther

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The cognitive impairments that are often observed in patients with alcohol use disorder (AUD) partially contribute to the extremely low rates of treatment initiation and adherence. Brain acetylcholine receptors (AChR) mediate and modulate cognitive and reward-related behavior and their distribution can be altered by long-term heavy drinking. Therefore, AChRs are promising pharmacotherapeutic targets for treating the cognitive symptoms of AUD. In the present study, the pro-cognitive efficacy of two AChR agonists, xanomeline and varenicline, were evaluated in group-housed monkeys who self-administered ethanol for more than one year. The muscarinic AChR antagonist scopolamine was used to disrupt performance of a serial stimulus discrimination and reversal (SDR) task designed to probe cognitive flexibility, defined as the ability to modify a previously learned behavior in response to a change in reinforcement contingencies. The ability of xanomeline and varenicline to remediate the disruptive effects of scopolamine was compared between dominant and subordinate monkeys, with lighter and heavier drinking histories, respectively. We hypothesized that subordinate monkeys would be more sensitive to all three drugs. Scopolamine dose-dependently impaired performance on the serial SDR task in all monkeys at doses lower than those that produced non-specific impairments (e.g, sedation); its potency did not differ between dominant and subordinate monkeys. However, both AChR agonists were effective in remediating the scopolamine-induced deficit in subordinate monkeys, but not in dominant monkeys. These findings suggest xanomeline and varenicline may be effective for enhancing cognitive flexibility in individuals with a history of heavy drinking.Significance statement: Pro-cognitive effects of two acetylcholine (Ach) receptor agonists were assessed in group-housed monkeys who had several years' experience drinking ethanol. The muscarinic ACh receptor agonist xanomeline and the nicotinic ACh receptor agonist varenicline reversed a cognitive deficit induced by the muscarinic ACh receptor antagonist scopolamine.

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The Use of Touchscreen-Based Methods to Characterize Effects of Psychoactive Drugs on Executive Function in Nonhuman Primates

Galbo-Thomma,

Czoty

2023

Curr. Pharmacol. Rep.

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Examining the effects of psychoactive drugs on complex behavioral processes in laboratory animals

Cited by 5 publications

References 161 publications

Cognitive performance as a behavioral phenotype associated with cocaine self-administration in female and male socially housed monkeys

Cognitive performance as a behavioral phenotype associated with cocaine self-administration in female and male socially housed monkeys

Cognitive-Enhancing Effects of Acetylcholine Receptor Agonists in Group-Housed Cynomolgus Monkeys Who Drink Ethanol

The Use of Touchscreen-Based Methods to Characterize Effects of Psychoactive Drugs on Executive Function in Nonhuman Primates

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