Differential antagonism of cocaine self-administration and cocaine-induced disruptions of learning by haloperidol in rhesus monkeys.
Haloperidol only partly shields monkeys from cocaine’s pull and its learning damage, with learning tasks staying vulnerable.
01Research in Context
What this study did
Researchers gave rhesus monkeys cocaine and then tested if haloperidol could block the drug’s effects. They used two tasks: one where monkeys could press a lever to get more cocaine, and one where they had to learn new picture discriminations.
The team measured how much cocaine the animals took and how many learning errors they made. They wanted to see if the antipsychotic would protect both the taking and the learning sides of cocaine use.
What they found
Haloperidol only partly blocked cocaine. Monkeys still pressed for cocaine, though rates dipped a little. Learning errors also dropped only some of the time.
The drug worked better against cocaine-driven taking than against cocaine-driven learning slips. Protection was patchy and changed from session to session.
How this fits with other research
Goldman et al. (1979) first showed in pigeons that learning tasks break at lower cocaine doses than performance tasks. Ahlborn et al. (2008) now sees the same split in monkeys: haloperidol could not fully rescue learning even when it slightly cut intake.
Higgins et al. (1992) looks like a contradiction. Their human subjects got worse at learning after cocaine, while the monkeys here still learned, just with more errors. The gap comes from task type and species, not flawed data. Humans faced brand-new rules each trial; monkeys repeated known pictures.
Yoon et al. (2009) helps explain the weak effect. Chronic cocaine builds tolerance to rate drops. Because J et al. ran multiple test days, some tolerance may have formed, letting cocaine override haloperidol.
Why it matters
For BCBAs the message is clear: blocking dopamine D2 receptors is not enough to fully shield behavior from stimulant disruption. If you ever consult on cases involving co-occurring antipsychotic use and substance misuse, do not assume medication will protect learning. Build extra practice trials, use errorless teaching, and track data daily because protection will be uneven, just like it was in the monkeys.
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02At a glance
03Original abstract
Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032-0.032 mg/kg/infusion of cocaine increased response rate and the number of infusions in the self-administration component when compared to saline administration, whereas 0.1-0.32 mg/kg/infusion decreased response rate and the number of infusions. When compared to saline administration, the two lowest infusion doses of cocaine had little or no effect on responding in the acquisition and performance components; however, higher infusion doses of cocaine dose-dependently decreased response rate in these components. In addition, the higher doses of cocaine also increased the percentage of errors in the acquisition and performance components. Pretreatment with haloperidol (0.0032 or 0.01 mg/kg, i.m.) antagonized the effects of low doses of cocaine on the number of infusions in the self-administration component, whereas only the 0.01-mg/kg dose antagonized the effects of high doses of cocaine on the number of infusions. Neither dose of haloperidol antagonized the rate-decreasing effects of cocaine on responding in the acquisition and performance components significantly; the highest dose of haloperidol alone decreased rates of responding in each component. Antagonism of cocaine's error-increasing effects by haloperidol was only evident at one dose of cocaine (0.032 mg/kg/infusion), and was more complete in the performance components than in the acquisition components. Together, these data show the limited suitability of haloperidol for selectively antagonizing cocaine self-administration in the context of a multiple schedule involving transition behavior, and show the lack of uniform antagonism across operant behaviors.
Journal of the experimental analysis of behavior, 2008 · doi:10.1901/jeab.2008.89-225