Interactive effects of morphine and dopaminergic compounds on spatial working memory in rhesus monkeys

Abstract

Opiates and dopamine (DA) play key roles in learning and memory in humans and animals. Although interactions between these neurotransmitters have been found, their functional roles remain to be fully elucidated, and their dysfunction may contribute to human diseases and addiction. Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus (WGTA) delayed-response task. Morphine and DA agonists (SKF-38393, apomorphine and bromocriptine) or DA antagonists (SKF-83566, haloperidol and sulpiride) were co-administered to the monkeys 30 min prior to the task. We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone. For example, morphine at 0.01 mg/kg impaired spatial working memory, while morphine (0.01 mg/kg) and apomorphine (0.01 or 0.06 mg/kg) co-treatment ameliorated this effect. Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys. A better understanding of these interactive relationships may provide insights into human addiction.

Developmental and behavioral alterations in zebrafish embryonically exposed to valproic acid (VPA): An aquatic model for autism

“…The lowest dose VPA group showed more significant changes compared to higher doses under these ASD-like behavioral assays, which may be due to the elevated VPA doses having greater potential for toxic effects. An additional reason may be the non-monotonic neurobehavioral effects which have previously been observed for many classes of compounds, such as endocrine disruptors (Lagarde et al, 2015), or dopaminergic compounds (Wang, J.-H. et al, 2013). The reason may arise from numerous molecular mechanisms such as opposing effects, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation.…”

“…The distance moved after touching was scored manually with one perimeter of the well as 1 mm, and a semiquantitative assessment of one to three quarters of the well as 0.25, 0.5 and 0.75 mm. There were a total of 30 embryos in each treatment group from three biological repeats that were used for data analysis with methods previously described in detail (Wang, X. et al, 2013; Yang et al, 2011).…”

A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys

“…While the small sample size is a limitation of this study because the pilot studies are often used before larger studies. In addition, individual differences in rhesus monkeys have been shown with small sample sizes in previous behavioral studies53132 in order to provide a foundation for further work with larger sample populations.…”

The Effects of Four Compounds That Act on the Dopaminergic and Serotonergic Systems on Working Memory in Animal Studies; A Literature Review

“…Three out of the four articles identified for bromocriptine concluded that bromocriptine led to improved working memory in different types of maze tests [ 23 , 24 , 25 ]. The fourth study analyzed the effects of bromocriptine on memory-depleted rhesus monkeys and the authors concluded that bromocriptine impaired working memory both individually and paired with morphine [ 26 ]. Tarantino et al [ 23 ], compared the effects of a SKF 38393, a D1 receptor agonist, with the effects of bromocriptine on working memory and reference memory in 12 mice.…”