Brain and Body Hyperthermia Associated with Heroin Self-Administration in Rats

Abstract

Intravenous heroin self-administration in trained rats was accompanied by robust brain hyperthermia (ϩ2.0-2.5°C); parallel changes were found in the dorsal and ventral striatum, mediodorsal thalamus, and deep temporal muscle. Temperature began to increase at variable latency after a signal of drug availability, increased reliably (ϳ0.4°C) before the first lever press for heroin, increased further (ϳ1.2°C) after the first heroin injection, and rose more slowly after the second and third injections to stabilize at an elevated plateau (39-40°C) for the remainder of the session. Brain and body temperature declined slowly when drug self-administration was terminated; naloxone precipitated a much more rapid decrease to baseline levels. Changes in temperature were similar across repeated daily sessions, except for the increase associated with the first selfadministration of each session, which had progressively shorter latency and greater acceleration. Despite consistent biphasic fluctuations in movement activity associated with heroin selfadministrations (gradual increase preceding the lever press, followed by an abrupt hypodynamia after drug infusion), mean brain temperature was very stable at an elevated plateau. Only mean muscle temperature showed evidence of biphasic fluctuations (Ϯ0.2°C) that were time locked to and correlated with lever pressing and associated movements. Drug-and behaviorrelated changes in brain temperature thus appear to reflect some form of neuronal activation, and, because temperature is a factor capable of affecting numerous neural functions, it may be an important variable in the control of behavior by drugs of abuse. Key words: brain temperature; opiates; heroin; neural activation; drug-taking behavior; thermorecording in behaving animalsAlthough it is generally assumed that brain temperature is a strictly regulated homeostatic variable with a range of fluctuations more restricted than those of body temperature (Satinoff, 1978;Bullock et al., 2001), relatively large increases in brain temperature (1.0 -2.0°C) have been found in animals exposed to various biologically significant stimuli or engaged in different behaviors. Temperature in different brain structures increases during exploration of new environment, treadmill running and swimming (Moser et al., 1993), feeding (Abrams and Hammel, 1964), and handling by an experimenter (Delgado and Hanai, 1966). Brain temperature also significantly differs between day and night, phasically rising during movement episodes (i.e., drinking, feeding, and running) and falling during sleep (Abrams and Hammel, 1965); it shows significant correlation with EEG during transition between sleep and wakefulness, as well as after environmental stimulation (Delgado and Hanai, 1966). Because many variables underlying neuronal excitability [i.e., membrane potential (Thompson et al., 1985), transport via ion-selective channels (Rosen, 2001), and amplitude and duration of single-unit spikes (Thompson et al., 1985;Erickson et al., 1996)] are temperature dependent, ch...

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Brain temperature effects of intravenous heroin: State dependency, environmental modulation, and the effects of dose

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