Although striatal neurons receive continuous dopamine (DA) input, little information is available on the role of such input in regulating normal striatal functions. To clarify this issue, we assessed how systemic administration of selective D1 and D2 receptor blockers or their combination alters striatal neuronal processing in freely moving rats. Single-unit recording was combined with iontophoresis to monitor basal impulse activity of dorsal and ventral striatal neurons and their responses to glutamate (GLU), a major source of excitatory striatal drive, and DA. SCH-23390 (0.2 mg/kg), a D1 antagonist, strongly elevated basal activity and attenuated neuronal responses to DA compared with control conditions, but GLU-induced excitations were enhanced relative to control as indicated by a reduction in response threshold, an increase in response magnitude, and a more frequent appearance of apparent depolarization inactivation. In contrast, the D2 antagonist eticlopride (0.2 mg/kg) had a weak depressing effect on basal activity and was completely ineffective in blocking the neuronal response to DA. Although eticlopride reduced the magnitude of the GLU response, the response threshold was lower, and depolarization inactivation occurred more often relative to control. The combined administration of these drugs resembled the effects of SCH-23390, but whereas the change in basal activity and the GLU response was weaker, the DA blocking effect was stronger than SCH-23390 alone. Our data support evidence for DA as a modulator of striatal function and suggest that under behaviorally relevant conditions tonically released DA acts mainly via D1 receptors to provide a continuous inhibiting or restraining effect on both basal activity and responsiveness of striatal neurons to GLUmediated excitatory input.

Hyperthermia is a symptom of methamphetamine (METH) intoxication and a factor implicated in neurotoxicity during chronic METH use. To characterize the thermic response to METH, it was injected once daily into rats at increasing doses (0, 1, 3, and 9 mg/kg, s.c.) while brain [nucleus accumbens (NAcc), hippocampus] and body (deep temporal muscle) temperatures were continuously monitored. METH produced dose-dependent hyperthermia, with brain structures (especially the NAcc) showing a more rapid and pronounced temperature increase than the muscle. At the highest dose, brain and body temperatures increased 3.5-4.0°C above basal levels and remained elevated for 3-5 hr. Stressful and other high-activity situations such as interaction with a conspecific female are also known to induce a significant hyperthermic response in the rat. A combination of social interaction and METH administration was tested for additive effects. Male rats were exposed daily to a conspecific female for a total of 120 min, and METH was injected at the same doses 30 min after the initial contact with the female. An initial hyperthermic response (ϳ1.5°C) to social interaction was followed by a large and prolonged hyperthermic response (3.5-5.0°C, 5-7 hr at 9 mg/kg) to METH, which was again stronger in brain structures (especially in the NAcc) than in the muscle. Although the combined effect of the hyperthermic events was not additive, METH administration during social interaction produced stronger and longer-lasting increases in brain and body temperature than that induced by drug alone, heating the brain in some animals near its biological limit (Ͼ41°C).

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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...