Role of brain dynorphin in nitrous oxide antinociception in mice.

Earlier studies indicate that nitrous oxide antinociception is mediated by opioid receptors, and we have hypothesized that nitrous oxide stimulates a neuronal release of an endogenous opioid peptide (EOP) that stimulates opioid receptors. To further test this hypothesis, male NIH Swiss mice were pretreated intracerebroventricularly with rabbit antisera to opioid peptides or with various inhibitors of peptidases involved in the degradation of EOPs. Mice were subsequently exposed to three different concentrations of nitrous oxide in oxygen, and their antinociceptive responsiveness was measured using the acetic acid abdominal constriction test. Nitrous oxide antinociception was significantly attenuated by 24-h pretreatment with antisera to various fragments of dynorphin (DYN) but not by antisera against methionine-enkephalin (ME) or beta-endorphin (beta-EP). In other experiments, nitrous oxide antinociception was significantly enhanced by 30-min pretreatment with phosphoramidon, an inhibitor of endopeptidase 24.11, which has been implicated in DYN degradation, but not bestatin or captopril, which inhibit aminopeptidase and angiotensin-converting enzyme, respectively. The latter enzymes have been implicated in degradation of certain EOPs albeit not DYN. These findings support the hypothesis that nitrous oxide antinociception in the mouse abdominal constriction test is mediated by endogenous DYN acting in the central nervous system.

The effects of atypical antipsychotics and phencyclidine (PCP) on rotorod performance.

A series of six experiments were conducted to determine the effects of haloperidol, clozapine, olanzapine, and phencyclidine (PCP) on rotorod performance. Rodents were trained to walk on a rotorod to avoid a mild shock to a criterion of 20 rpm for 3 min. None of the vehicles of any of these drugs disrupted rotorod performance. Haloperidol disrupted rotorod performance at doses of 0.03, 0.1, and 0.3 mg/kg, and olanzapine disrupted rotorod performance at doses of 3.0 and 10.0 mg/kg. Clozapine produced a much milder disruption across all three doses (3.0, 10.0, and 30.0 mg/kg). PCP produced a consistent and severe disruption of rotorod performance at doses of 4.0 and 6.0 mg/kg, but not at a dose of 2.0 mg/kg. Twenty-four hours postinjection there were no residual PCP effects on rotorod performance. Coadministration of either haloperidol or olanzapine with PCP did not reverse PCP-induced disruption in rotorod performance, while clozapine produced a partial reversal at only one dose. These findings indicate that olanzapine functions similarly to classic antipsychotics with respect to their effects on locomotion and balance.