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

Abstract

Here we examined how intravenous heroin at a dose that maintains self-administration (0.1 mg/kg) affects brain temperature homeostasis in freely moving rats under conditions that seek to mimic some aspects of human drug use. When administered under standard laboratory conditions (quiet rest at 22°C ambient temperature), heroin induced moderate temperature increases (1.0–1.5°C) in the nucleus accumbens (NAc), a critical structure of the brain motivation-reinforcement circuit. By simultaneously recording temperatures in the temporal muscle and skin, we demonstrate that the hyperthermic effects of heroin results primarily from inhibition of heat loss due to strong and prolonged skin vasoconstriction. Heroin-induced brain temperature increases were enhanced during behavioral activation (i.e., social interaction) and in a moderately warm environment (29°C). By calculating the “net” effects of the drug in these two conditions, we found that this enhancement results from the summation of the hyperthermic effects of heroin with similar effects induced by either social interaction or a warmer environment. When the dose of heroin was increased (to 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 mg/kg), brain temperature showed a biphasic down-up response. The initial temperature decrease was dose-dependent and resulted from a transient inhibition of intra-brain heat production coupled with increased heat loss via skin surfaces—the effects typically induced by general anesthetics. These initial inhibitory effects induced by large-dose heroin injections could be related to profound CNS depression—the most serious health complications typical of heroin overdose in humans.

No evidence of abnormal metabolic or inflammatory activity in the brains of patients with rheumatoid arthritis: results from a preliminary study using whole-brain magnetic resonance spectroscopic imaging (MRSI)

“…Two human studies have found reduced NAA in frontal gray matter in opioid addicted individuals [39,40]. Several animal studies have reported temperature changes in the nucleus accumbens following intravenous opioid administration [41][42][43]. Therefore, there is the potential for a medication confound in the present study.…”

Brain temperature and its role in physiology and pathophysiology: Lessons from 20 years of thermorecording

“…Therefore, it could be assumed that heroin should induce brain hypothermiaa response opposite to that induced by cocaine and other psychostimulants. However, we found that iv heroin passively administered to awake, quietly resting rats at a low self-administering dose (0.1 mg/ kg) induces moderate increases in NAc and muscle temperatures (Figure 25) that were comparable in magnitude but longer in duration than those induced by iv cocaine [228]. While the increases in brain and muscle temperatures were generally correlative, their difference, the NAc-muscle differential, significantly increased between~10 and~50 min post-injection, with a peak at~20 min (Figure 25).…”

“…However, with increase in doses, the response became biphasic, with the initial, dose-dependent temperature decreases and subsequent temperature increases. Data were replotted from [228].…”

“…When heroin was injected at 29•C ambient temperatures, drug-induced temperature elevation became more prolonged. Data were replotted from [228]. more evident and significant when the rat received a double-dose heroin injection instead of the regular 0.1 mg/kg injection (Figure 27(e)).…”

Changes in brain oxygen and glucose induced by oxycodone: Relationships with brain temperature and peripheral vascular tone

“…Surgical procedures for thermorecording experiments have been described in detail elsewhere (Kiyatkin et al, 2013; Bola and Kiyatkin, 2017). In brief, under the same general anesthesia protocol, rats were implanted with a jugular catheter and three copper-constantan thermocouple electrodes in the NAc shell (AP +1.2mm, M-L: ±0.8 mm, DV +7.4 mm), temporal muscle, and subcutaneously along the nasal ridge with the tip ∼15 mm anterior to bregma.…”