Evaluation of the Reinforcing Effect of Quetiapine, Alone and in Combination with Cocaine, in Rhesus Monkeys

Abstract

There are several case reports of nonmedicinal quetiapine abuse, yet there are very limited preclinical studies investigating quetiapine self-administration. The goal of this study was to investigate the reinforcing effects of quetiapine alone and in combination with intravenous cocaine in monkeys. In experiment 1, cocaine-experienced female monkeys (N 5 4) responded under a fixed-ratio (FR) 30 schedule of food reinforcement (1.0-g banana-flavored pellets), and when responding was stable, quetiapine (0.003-0.1 mg/kg per injection) or saline was substituted for a minimum of five sessions; there was a return to food-maintained responding between doses. Next, monkeys were treated with quetiapine (25 mg, by mouth, twice a day) for approximately 30 days, and then the quetiapine selfadministration dose-response curve was redetermined. In experiment 2, male monkeys (N 5 6) self-administered cocaine under a concurrent FR schedule with food reinforcement (three food pellets) as the alternative to cocaine (0.003-0.3 mg/kg per injection) presentation. Once choice responding was stable, the effects of adding quetiapine (0.03 or 0.1 mg/kg per injection) to the cocaine solution were examined. In experiment 1, quetiapine did not function as a reinforcer, and chronic quetiapine treatment did not alter these effects. In experiment 2, cocaine choice increased in a dose-dependent fashion. The addition of quetiapine to cocaine resulted in increases in lowdose cocaine choice and number of cocaine injections in four monkeys, while not affecting high-dose cocaine preference. Thus, although quetiapine alone does not have abuse potential, there was evidence of enhancement of the reinforcing potency of cocaine. These results suggest that the use of quetiapine in cocaine-addicted patients should be monitored.

Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review

“…Prison inmates and opioid addicts seem to represent the most at-risk populations [ 24 , 75 , 76 , 95 , 96 , 97 ]. Quetiapine psychotropic effects [ 86 , 87 ] are associated with both increased levels of DA in the nucleus accumbens (NAc) area [ 89 , 98 , 99 , 100 ] and D2 receptor blockage. As some pharmacodynamic mechanisms are shared by other non-misused SGAs [ 101 , 102 , 103 , 104 ], other factors [ 105 , 106 ] or pharmacological effects explaining the molecule misuse potential may include norquetiapine-related norepinephrine reuptake blockade [ 75 ], 5-HT7 antagonist properties and sigma receptor activation [ 107 , 108 ].…”

Is There a Potential of Misuse for Quetiapine?

“…Overall, the recreational drugs' 'high' has been associated with increased levels of dopamine in the nucleus accumbens (NAc) shell/mesolimbic areas [15] and, similar to remaining antipsychotics, quetiapine blocks dopamine D2 receptors [16]. However, quetiapine, but not olanzapine, may increase DA levels [39], preferentially in the NAc shell [40], with some data [41] suggesting as well a quetiapine-associated enhancement of cocaine reinforcing potency. Conversely, mechanisms like fast dissociation from dopamine receptors [12; 42-43]; and prefrontal dopamine release mediated by 5-HT 1A receptor activation and 5-HT 2A inhibition [44], putatively explaining some recreational effects, are shared by other, non-misusing, SGAs [45].…”

Analysis and Annotation of DNA Methylation in Two Nonhuman Primate Species Using the Infinium Human Methylation 450K and EPIC BeadChips

“…Rhesus macaques are for instance frequently used for the development of vaccines against infectious diseases, including Sars-CoV-2, HIV, influenza and ebola virus [22][23][24][25][26]. They are also widely used in various studies ranging from development and imprinting, to addiction and social cognition [27][28][29][30][31][32]. In parallel, the Chlorocebus genus, among which figure prominently African green monkeys (AGMs), have been a gold standard model for investigation of several infectious diseases, such as yellow fever, trypanosoma and plague in the past [33,34].…”