Involvement of dopamine D3 and D4 receptors in the discriminative stimulus properties of cocaine in the rat.

The present study was carried out to determine the involvement of dopamine receptor subtypes D3 and D4, in the discriminative stimulus effects of cocaine in the rats trained to discriminate 10 mg/kg of cocaine from vehicle. The discriminative stimulus effects of cocaine (1-10 mg/kg) were dose-dependent. The dopamine D2 receptor agonist bromocriptine (1.25-20 mg/kg) and the dopamine D3 receptor agonist R(+)-7-OH-DPAT (0.0001-0.3 mg/kg) produced cocaine (10 mg/kg)-like discriminative stimulus effects. Both the dopamine D3 receptor antagonist GR103691 (1 mg/kg) and the dopamine D4 receptor antagonist L745870 (1 mg/kg) partially antagonized the discriminative stimulus effects of cocaine (10 mg/kg) and the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). L745870 (0.001 mg/kg) inhibited the antagonistic effects of GR103691 (1 mg/kg) on the discriminative stimulus effects of cocaine (10 mg/kg), whereas the drug (0.001 mg/kg) enhanced the antagonistic effects of GR103691 (1 mg/kg) on the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). GR103691 (1 mg/kg) in combination with L745870 (0.001 mg/kg) did not markedly affect the cocaine (10 mg/kg)-like discriminative stimulus effects of bromocriptine (20 mg/kg). These results suggest that the discriminative stimulus effects of cocaine are different from the cocaine-like discriminative stimulus effects of bromocriptine or R(+)-7-OH-DPAT, in terms of dopamine D3 and D4 receptors.

Tail-swing behavior: a novel animal model for anxiety.

The present study was designed to examine the effects of diazepam, nitrazepam, desipramine and haloperidol on tail-swing behavior in mice and to characterize the effects of diazepam. Mice were suspended with rubber bands tied around their upper bodies in order to force their heads upwards. The duration of tail-swing behavior was then measured. Diazepam (0.3 and 1 mg/kg) and nitrazepam (0.3 and 1 mg/kg) significantly depressed tail-swing behavior, while they did not affect ambulation or muscle tone. In contrast, desipramine (10-30 mg/kg) did not affect tail-swing behavior, but at doses of 17.5 and 30 mg/kg produced a marked reduction in ambulation. Haloperidol (0.15 mg/kg) significantly decreased both tail-swing behavior and ambulation. The benzodiazepine receptor antagonist flumazenil (1 and 10 mg/kg), the benzodiazepine receptor inverse agonist beta-carboline-3-carboxylic acid N-methylamide (beta-CCM; 3 mg/kg) and the GABA(A) receptor antagonist bicuculline (3 mg/kg) reversed the effects of diazepam (1 mg/kg) on tail-swing behavior, although administered alone they failed to influence such behavior. These results suggest that anxiety and/or fear are responsible for tail-swing behavior.

Natural killer activity and serum immunosuppressive acidic protein levels in esophageal and gastric cancers.

The natural killer (NK) activity of peripheral blood mononuclear cells and serum immunosuppressive acidic protein (IAP) levels were examined in patients with esophageal or gastric cancer, before and after surgery. Patients with stage IV esophageal or stage IV gastric cancer had significantly lower NK activity (39.5 +/- 14.8% and 37 +/- 11.6%, respectively), and also higher serum IAP levels (778 +/- 264 micrograms/mL and 633 +/- 156 micrograms/mL, respectively), than the corresponding control values (50 +/- 5.6% and 375 +/- 26 micrograms/mL, respectively). Patients with esophageal or gastric cancer who underwent curative resection had high NK activity (54.8 +/- 11.6% and 54.8 +/- 8.0%, respectively), and low IAP levels (471 +/- 116 micrograms/mL and 490 +/- 42 micrograms/mL, respectively), compared with those who underwent non-curative resection. Patients who underwent non-curative resection had lower NK activity and higher serum IAP levels than those who underwent curative resection, even 1 month after surgery. Mononuclear cells in the regional lymph nodes and tumor specimens showed significantly lower NK activity than those in the peripheral blood and spleen. Thus, NK activity and the IAP level reflected the immunocompetence, clinical course, and surgical curability of those patients. NK cells appeared not to have any significant antitumor activity in the regional lymph nodes or in the tumor itself, although they were still active in the peripheral blood.

[A case of recurrent pelvic tumor of sigmoid colon cancer showing partial response to lipiodolization].

We performed lipiodolization and immunochemotherapy for recurrent pelvic tumor of sigmoid colon cancer using an infuserport which was implanted and connected to the catheter placed in the right internal iliac artery. Following lipiodolization, the level of CEA (980 ng/ml) decreased to within the normal range. MRI showed necrotic change and regression (more than 50%) of tumor. DSA revealed disappearance of tumor neovascularity. No serious side effect but skin erosion in the gluteal region was encountered after lipiodolization. This result suggests that lipiodolization is worth performing in further clinical trials for pelvic tumor.