Temporal factors affecting cocaine-opioid interactions: a cocaine drug discrimination study in rats.

Abstract:

RATIONALE:Increasing concomitant abuse of cocaine and morphine-like opioids has prompted a number of studies aimed at understanding how these drugs interact. OBJECTIVE:The present study was designed to determine if variations in opioid pretreatment time would affect how mu opioid agonists interact with cocaine. METHODS:Rats were trained to discriminate 10 mg/kg cocaine from saline. One group of subjects (n=6) received morphine (5.6 mg/kg) 0.5 h, 1 h or 4 h prior to cumulative doses of cocaine (0.1-17.8 mg/kg). These pretreatment times were selected to overlap with states of acute opioid tolerance (approximately 1 h) or acute opioid dependence (approximately 4 h) as demonstrated by previous studies. A second group (n=6) was administered naloxone (0.3 mg/kg) 5 min prior to cumulative cocaine doses, with or without a 4-h morphine (5.6 mg/kg) or methadone (3.0 mg/kg) pretreatment. In a third procedure, the same subjects used in the second experiment were also tested for time-dependent changes in the analgesic effect of morphine using a hot-plate assay. RESULTS:Morphine pretreatment 1 h prior to assessment of the cocaine dose-response function significantly enhanced the discriminative stimulus effects of cocaine. However, neither 0.5-h or 4-h morphine pretreatment had any effect. In contrast, when naloxone was administered 4 h following either morphine or methadone and 5 min prior to assessment of the cocaine dose-response curve, the discriminative stimulus effects of cocaine were significantly attenuated. In assessing morphine-induced analgesia, paw-lick latency was significantly longer at 1 h and shorter at 4 h following morphine administration. CONCLUSIONS:The results illustrate the importance of temporal parameters for interactions between cocaine and mu opioid agonists.

journal_title

Psychopharmacology

authors

Green-Jordan K,Warren L,Kantak KM

doi

10.1007/s002130100732

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

427-34

issue

4

eissn

0033-3158

issn

1432-2072

journal_volume

156

pub_type

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