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Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen

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Abstract

Rationale

Acute and/or chronic exposure to cocaine can affect cognitive performance, which may influence rate of recovery during treatment.

Objective

Effects of the GABA-B receptor agonist baclofen were assessed for potency to reverse the negative influence of acute, pre-session, intravenous (IV) injection of cocaine on cognitive performance in Macaca mulatta nonhuman primates.

Methods

Animals were trained to perform a modified delayed match to sample (DMS) task incorporating two types of trials with varying degrees of cognitive load that had different decision requirements in order to correctly utilize information retained over the delay interval. The effects of cocaine (0.2, 0.4, and 0.6 mg/kg, IV) alone and in combination with baclofen (0.29 and 0.40 mg/kg, IV) were examined with respect to sustained performance levels. Brain metabolic activity during performance of the task was assessed using PET imaged uptake of [18 F]-fluorodeoxyglucose.

Results

Acute cocaine injections produced a dose-dependent decline in DMS performance selective for trials of high cognitive load. The GABA-receptor agonist baclofen, co-administered with cocaine, reversed task performance back to nondrug (saline IV) control levels. Simultaneous assessment of PET-imaged brain metabolic activity in prefrontal cortex (PFC) showed alterations by cocaine compared to PFC metabolic activation in nondrug (saline, IV) control DMS sessions, but like performance, PFC activation was returned to control levels by baclofen (0.40 mg/kg, IV) injected with cocaine.

Conclusions

The results show that baclofen, administered at a relatively high dose, reversed the cognitive deficits produced by acute cocaine intoxication that may have implications for use in chronic drug exposure.

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Acknowledgments

We appreciate the technical assistance from the following individuals in the above studies: Joshua Long, Joseph Noto, Brian Parrish, Mack Miller, and Michael Todd. This work was supported by NIH grants DA023573, DA06634, and DA026487

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, 27157, USA

    Linda J. Porrino, Robert E. Hampson, Ioan Opris & Samuel A. Deadwyler

  2. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157-1083, USA

    Samuel A. Deadwyler

Authors
  1. Linda J. Porrino
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  2. Robert E. Hampson
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  3. Ioan Opris
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  4. Samuel A. Deadwyler
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Correspondence to Samuel A. Deadwyler.

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Porrino, L.J., Hampson, R.E., Opris, I. et al. Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen. Psychopharmacology 225, 105–114 (2013). https://doi.org/10.1007/s00213-012-2798-6

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  • DOI: https://doi.org/10.1007/s00213-012-2798-6

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