Premium
Subject‐regulated dosing alters morphine self‐administration behavior and morphine‐stimulated [ 35 S]GTPγS binding
Author(s) -
Kruzich P.J.,
Chen A.C.H.,
Unterwald E.M.,
Kreek M.J.
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10173
Subject(s) - morphine , dosing , self administration , pharmacology , gtp' , medicine , saline , dose–response relationship , opioid , anesthesia , receptor , chemistry , biochemistry , enzyme
Repeated intake of opioids is associated with dose escalation and alterations in signal transduction at the G‐protein‐coupled receptor level. The current study utilized two experiments to identify factors in rats that influence consumption rates such as daily intake of self‐administered morphine and receptor desensitization. In Experiment 1, rats self‐administered either 0.30, 1.00, or 3.00 mg/kg/infusion morphine sulfate (morphine) during 7 daily 4‐h sessions. For Experiment 2, rats were assigned to groups that self‐administered either 1) self‐regulated escalating doses of morphine, 2) a fixed dose of morphine, or 3) saline during 18‐h sessions for 7 days to determine if dose control would increase consumption without significantly decreasing response rate. We then assessed morphine‐stimulated [ 35 S]GTPγS binding in the amygdala and thalamus from these three groups in Experiment 2. Results from Experiment 1 demonstrated that 0.30 mg/kg/morphine did not support stable self‐administration. For Experiment 2, the self‐escalation group self‐administered more morphine than the fixed‐dose group, yet maintained similar response rates. Additionally, self‐escalation rats demonstrated decreased morphine‐stimulated [ 35 S]GTPγS binding in membranes prepared from amygdalar and thalamic nuclei compared to the fixed‐dose and control groups. Our results suggest that session length inversely affects consumption rates for fixed doses of morphine. Self‐regulated dosing of morphine is also associated with rapid escalation of daily consumption and no significant alterations in consumption rates. These results suggest subject‐regulated dosing is a useful approach for modeling dose escalation associated with opioid dependence. Synapse 47:243–249, 2003. © 2003 Wiley‐Liss, Inc.