sr-59230a and Fever

The rodents exposed to repeated cold stress according to a specific schedule, known as specific alternation of rhythm in temperature (SART), exhibit autonomic imbalance, and is now used as an experimental model of fibromyalgia. To explore the susceptibility of SART-stressed animals to novel acute stress, we tested whether exposure of mice to SART stress for 1 week alters the extent of acute restraint stress-induced hyperthermia. Mice were subjected to 7-d SART stress sessions; i.e., the mice were alternately exposed to 24 and 4°C at 1-h intervals during the daytime (09:00-16:00) and kept at 4°C overnight (16:00-09:00). SART-stressed and unstressed mice were exposed to acute restraint stress for 20-60 min, during which rectal temperature was monitored. Serum corticosterone levels were measured before and after 60-min exposure to restraint stress. SART stress itself did not alter the body temperature or serum corticosterone levels in mice. Acute restraint stress increased the body temperature and serum corticosterone levels, both responses being greater in SART-stressed mice than unstressed mice. The enhanced hyperthermic responses to acute restraint stress in SART-stressed mice were significantly attenuated by SR59230A, a β

Topics: Adipose Tissue, Brown; Adrenergic beta-3 Receptor Antagonists; Animals; Anti-Anxiety Agents; Cold Temperature; Corticosterone; Diazepam; Fever; Male; Mice; Mifepristone; Propanolamines; Receptors, Glucocorticoid; Restraint, Physical; Stress, Physiological; Stress, Psychological; Uncoupling Protein 1

Body temperature increases when individuals experience salient, emotionally significant events. There is controversy concerning the contribution of nonshivering thermogenesis in brown adipose tissue (BAT) to emotional hyperthermia. In the present study we compared BAT, core body, and brain temperature, and tail blood flow, simultaneously measured, to determine whether BAT thermogenesis contributes to emotional hyperthermia in a resident Sprague-Dawley rat when an intruder rat, either freely-moving or confined to a small cage, is suddenly introduced into the cage of the resident rat for 30 min. Introduction of the intruder rat promptly increased BAT, body, and brain temperatures in the resident rat. For the caged intruder these temperature increases were 1.4 ± 0.2, 0.8 ± 0.1, 1.0 ± 0.1°C, respectively, with the increase in BAT temperature being significantly greater (P < 0.01) than the increases in body and brain. The initial 5-min slope of the BAT temperature record (0.18 ± 0.02°C/min) was significantly greater (P < 0.01) than the corresponding value for body (0.10 ± 0.01°C/min) and brain (0.09 ± 0.02°C/min). Tail artery pulse amplitude fell acutely when the intruder rat was introduced, possibly contributing to the increases in body and brain temperature. Prior blockade of β3 adrenoceptors (SR59230A 10 mg/kg ip) significantly reduced the amplitude of each temperature increase. Intruder-evoked increases in BAT temperature were similar in resident rats maintained at 11°C for 3 days. In the caged intruder situation there is no bodily contact between the rats, so the stimulus is psychological rather than physical. Our study thus demonstrates that BAT thermogenesis contributes to increases in body and brain temperature occurring during emotional hyperthermia.

Topics: Adipose Tissue, Brown; Adrenergic beta-3 Receptor Antagonists; Aggression; Animals; Body Temperature; Emotions; Fever; Male; Propanolamines; Pulsatile Flow; Rats; Rats, Sprague-Dawley; Stress, Psychological; Tail; Territoriality; Thermogenesis

We have investigated the ability of the beta(3)-adrenoceptor antagonist 1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4,-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol hydrochloride (SR59230A) to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and whether alpha(1)-adrenoceptor antagonist actions are involved.. Mice were implanted with temperature probes under anaesthesia, and allowed 2 week recovery. MDMA (20 mg x kg(-1)) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry.. Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.8 degrees C at 130 min post injection. A low concentration of SR59230A (0.5 mg x kg(-1)) produced a small but significant attenuation of the slowly developing hyperthermia to MDMA. A high concentration of SR59230A (5 mg x kg(-1)) revealed a significant and marked early hypothermic reaction to MDMA, an effect that was mimicked by the alpha(1)-adrenoceptor antagonist prazosin. Functional and ligand binding studies revealed actions of SR59230A at alpha(1)-adrenoceptors.. 1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4,-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol hydrochloride in high concentrations modulates the hyperthermic actions of MDMA in mice in two ways: by blocking an early alpha(1)-adrenoceptor-mediated component to reveal a hypothermia, and by a small attenuation of the later hyperthermic component which may possibly be beta(3)-adrenoceptor-mediated (this seen with the low concentration of SR59230A). Hence, the major actions of SR59230A in modulating the actions of MDMA on temperature involve alpha(1)-adrenoceptor antagonism.

Topics: Adrenergic beta-3 Receptor Antagonists; Animals; Body Temperature; Fever; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; N-Methyl-3,4-methylenedioxyamphetamine; Propanolamines; Protein Binding; Rats; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, beta-3

1. Studies were designed to examine the effects of alpha(1) (alpha(1)AR)- plus beta(3)-adrenoreceptor (beta(3)AR) antagonists on 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced hyperthermia and measures of rhabdomyolysis (creatine kinase (CK)) and renal function (blood urea nitrogen (BUN) and serum creatinine (sCr)) in male Sprague-Dawley rats. 2. MDMA (40 mg x kg(-1), s.c.) induced a rapid and robust increase in rectal temperature, which was significantly attenuated by pretreatment with the alpha(1)AR antagonist prazosin (100 microg x kg(-1), i.p.) plus the beta(3)AR antagonist SR59230A (5 mg x kg(-1), i.p.). 3. CK levels significantly increased (peaking at 4 h) after MDMA treatment and were blocked by the combination of prazosin plus SR59230A. 4. At 4 h after MDMA treatment, BUN and sCr levels were also significantly increased and could be prevented by this combination of alpha(1)AR- plus beta(3)AR-antagonists. 5. The results from this study suggest that alpha(1)AR and beta(3)AR play a critical role in the etiology of MDMA-mediated hyperthermia and subsequent rhabdomyolysis.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Antagonists; Animals; Blood Urea Nitrogen; Body Temperature; Creatine Kinase; Drug Administration Schedule; Drug Therapy, Combination; Fever; Injections, Intraperitoneal; Injections, Subcutaneous; Male; N-Methyl-3,4-methylenedioxyamphetamine; Prazosin; Propanolamines; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, beta-3; Rhabdomyolysis; Time Factors