The central serotonin 2B receptor: a new pharmacological target to modulate the mesoaccumbens dopaminergic pathway activity.

The function of the serotonin(2B) receptor (5-HT(2B)R) in the mammalian brain is poorly characterized, especially with regard to its influence on dopamine (DA) neuron activity. Here, we assessed this issue by evaluating effects of 5-HT(2B)Rs ligands in the control of striatal and accumbal DA outflow, using in vivo microdialysis in halothane-anesthetized rats, and amphetamine-induced hyperlocomotion in vigil rats. The selective 5-HT(2B)R antagonist 1-[(2-chloro-3,4-dimethoxyphenyl)methyl]-2,3,4,9-tetrahydro-6-methyl-1H-pyrido[3,4-B]indole (LY 266097; 0.16 mg/kg, i.p.) had no influence on basal accumbal and striatal DA outflow but reduced significantly accumbal DA outflow when injected at 0.63 mg/kg. A significant reduction of basal DA outflow in the nucleus accumbens was also observed after i.p. administration of 0.16 mg/kg 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine, another selective 5-HT(2B)R antagonist. In contrast, the 5-HT(2B)R agonist alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (3 mg/kg, s.c.) had no influence on basal DA outflow in either brain region. The increase in striatal and accumbal DA outflow induced by the 5-HT(2C)R inverse agonist 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole (5 mg/kg, i.p.) was unaltered by LY 266097 (0.63 mg/kg) pre-treatment. Conversely, LY 266097 (0.63 mg/kg) significantly diminished the increase in DA outflow induced by haloperidol (0.01 mg/kg, s.c.) or amphetamine (0.5 mg/kg, i.p.) in the nucleus accumbens, but not in the striatum. Amphetamine-induced hyperlocomotion (1 mg/kg) was also attenuated by LY 266097 (0.63 mg/kg). These findings demonstrate that 5-HT(2B)Rs exert a facilitatory control on mesoaccumbens DA pathway activity, and suggest that they may constitute a new target for improved treatment of DA-related neuropsychiatric disorders.

Single-dose dexamethasone reduces dynamic pain after total hip arthroplasty.

BACKGROUND: Preoperative glucocorticoids reduce postoperative nausea but may also improve analgesia and decrease opioid consumption. METHODS: Fifty consecutive patients undergoing elective, unilateral, primary total hip arthroplasty under spinal anesthesia with propofol sedation received in a randomized, double-blind, placebo-controlled manner either 40 mg of dexamethasone or saline placebo i.v. before the start of surgery. I.v. patient-controlled analgesia morphine, ibuprofen 400 mg p.o. q6 h and acetaminophen 650 mg p.o. q6 h were given for 48 h. Pain (0-10 numeric rating scale, NRS) at rest, side effects, and total cumulative patient-controlled analgesia morphine consumption were recorded q4 h for 48 h. Dynamic pain NRS score was recorded at 24 h. C-reactive protein levels were measured in a subgroup of 25 patients at 48 h. RESULTS: The intraoperative sedation requirement with propofol was significantly increased in the dexamethasone group (234.6 +/- 160.1 vs 138.8 +/- 122.7 mg, P = 0.02). Dynamic pain was greatly reduced in the dexamethasone group (NRS score: 2.7, 95% CI: 2.2-3.1 vs 6.8, 6.4-7.2; P < 0.0001). There was no significant effect on pain at rest or cumulative morphine consumption at any time. C-reactive protein levels at 48 h were markedly reduced by dexamethasone (52.4 mg/mL, 28.2-76.6 vs 194.2, 168.9-219.4; P < 0.0001). Seven patients in the control group, but only one in the dexamethasone group, were treated for nausea (P = 0.05). CONCLUSIONS: A single, preoperative i.v. dose of dexamethasone 40 mg has a prolonged suppressive effect on the inflammatory response and decreases dynamic pain 24 h after total hip arthroplasty.

Blood gas measurements using the Bayer Rapid Point 405: are we basing our decisions on accurate data?

OBJECTIVE: Therapeutic decisions in the Operating Room (OR) are often made based solely upon results obtained from arterial blood gas machines. We evaluated how precise and accurate the results obtained from Bayer Rapid Point 405 (RP405) were vis-à-vis those of our blood gas laboratory and if they met the standards of the members of the anesthesia department. METHODS: About 3 ml of blood from an indwelling arterial catheter were drawn into a heparinized syringe (FIMS Portex Inc.) from each of 90 patients and immediately analyzed by two RP405 and the hospital's main blood gas machines (Instrumentation Laboratories GEM 3000). The remaining 2.8 ml of blood was used to measure Hematocrit and sent to the hospital's main biochemistry laboratory for electrolyte measurement using an indirect ion selective method (Roche Diagnostics Modular ISE Module). A survey was distributed to each of the 19 anesthesiologists at the Sir Mortimer B Davis Jewish General Hospital (JGH). Their opinions for accuracy and treatment thresholds for each of the 12 variables measured by the RP405 were sought. RESULTS: For all measured variables, including pH, pCO2, pO2, potassium and Hematocrit, the correlation between the measurements from the RP405 and the gold standard were all above 95.5% with a p < 0.001. The survey results demonstrate that the machine gives results that are accurate within the acceptability frame expected by our staff anesthesiologists. CONCLUSION: Anesthesiologists must be confident that the information they receive is accurate in the context of rapidly changing clinical status. Our results show that the RP405 analyzers produce reliable measurements.