Study about how benzos affect cocaine use in monkeys

This study looked at the "abuse potential" of a compound thought to not enhance cocaine choice (less associated with abuse) that's similar to benzos and z-drugs but does not target a specific GABA receptor.  The compound is called L-838,417.  They allowed their subjects, rhesus monkeys, to choose between cocaine alone versus cocaine plus a benzo, a z-drug or L-838,417.  The monkeys were more likely to choose cocaine plus a benzo or a z-drug versus cocaine alone or versus cocaine plus L-838,417.  The cocaine plus L-838,417 choice was higher than cocaine alone but not as high as the other two cocaine mixtures.

I think this study is rather interesting.  I'm not very familiar with how "abuse potential" of certain drugs is studied.  It's a lot simpler than I imagined if most studies are like this one.

Journal: Psychopharmacology

Full title: "Self-administration of benzodiazepine and cocaine combinations by male and female rhesus monkeys in a choice procedure: role of α1 subunit-containing GABAA receptors."

Abstract

RATIONALE:

Compounds lacking efficacy at the α1 subunit-containing GABAA (α1GABAA) receptor appear to have reduced abuse potential compared with those having measurable efficacy at this receptor, though their self-administration in nonhuman primates is dependent upon past drug experience.

OBJECTIVES:

We used a drug vs. drug choice procedure to evaluate the hypothesis that L-838,417, a compound lacking efficacy at αGABAA receptors, would not enhance cocaine choice in monkeys trained to self-administer cocaine. We also hypothesized that zolpidem, a compound with preferential modulation of ⍺1GABAA receptors and midazolam, a nonselective benzodiazepine, would enhance cocaine choice in this procedure.

METHODS:

One female and three male rhesus monkeys chose between cocaine alone (0.1 mg/kg/injection) vs. the same dose of cocaine combined with midazolam (0.003-0.1 mg/kg/injection), zolpidem (0.003-0.3 mg/kg/injection), or L-838-417 (0.01-0.1 mg/kg/injection). In addition, we evaluated choice between saline and L-838,417 at select doses to determine whether L-838,417 would function as a reinforcer on its own.

RESULTS:

Consistent with our hypotheses, midazolam- and zolpidem-cocaine mixtures were chosen over cocaine alone at sufficiently high doses. However, L-838,417-cocaine mixtures also were chosen over cocaine alone in three of four subjects with at least one dose. When available alone vs. saline, L-838,417 did not function as a reinforcer in any subject.

CONCLUSION:

Compounds that lack efficacy at α1GABAA receptors may have low abuse potential compared to classic benzodiazepines, but self-administration of these compounds is context-dependent.

https://www.ncbi.nlm.nih.gov/pubmed/31183518