Effects of clozapine and haloperidol on baseline levels of vacuous jaw movements in aged rats.

Some studies have indicated that aged rats have elevated basal levels of vacuous jaw movements and these vacuous jaw movements are exacerbated by classic neuroleptic drugs like haloperidol, but the effects of the atypical antipsychotic clozapine on vacuous jaw movements in aged rats has not previously been studied. Aged rats were administered daily intraperitoneal injections of either haloperidol (0.04, 0.1 or 0.4 mg/kg), clozapine (0.4, 1.0, 4.0 mg/kg) or 0.3% tartaric acid vehicle for 22 days. On days 1, 8, 15 and 22 these rats were placed in an observation tube and vacuous jaw movements were recorded by two trained observers. Vacuous jaw movements were present in the aged rats receiving vehicle. Haloperidol produced a dose-dependent increase in vacuous jaw movements while clozapine produced a dose-dependent attenuation of vacuous jaw movements, relative to the vehicle-treated rats. These results indicate that screening for vacuous jaw movements may provide a useful behavioral assay for atypical antipsychotic drugs which do not produce extrapyramidal side effects and that clozapine's resistance to these side effects may extend to populations of elderly human patients.

The rewarding properties of NMDA and MK-801 (dizocilpine) as indexed by the conditioned place preference paradigm.

N-Methyl-D-aspartate (NMDA) ([R]-2-[Methylamino]succinic acid) is a specific excitatory amino acid. Two experiments were conducted to determine the rewarding properties of this compound using the conditioned place preference paradigm. In the first experiment, 40 male Sprague-Dawley rats received place preference conditioning for a 4 day period. The conditioned place preference apparatus consisted of two chambers with distinct visual and tactile cues, separated by a removable door. On days 2 and 4, rats were systemically administered NMDA (1.0, 15.0, and 30.0 mg/kg) paired with one chamber. On days 3 and 5, rats were systemically administered saline paired with the other chamber. Day 6 was the test day, and the rat was allowed free run of the entire apparatus in a drug-free state. Time spent in each side of the apparatus was computer recorded. NMDA produced a significant increase in the amount of time spent on the side previously paired with drug for 15.0 and 30.0, but not 1.0 mg/kg NMDA. In the second experiment, systemic administration of NMDA (30.0 mg/kg) paired with the noncompetitive NMDA receptor antagonist, MK-801 (0.5 mg/kg), resulted in neither place preference nor place aversion.

The effects of the naltrexone implant on rodent social interactions and cocaine-induced conditioned place preference.

Two experiments were conducted to determine the behavioral properties of the naltrexone implant on: 1) rodent social interactions; and 2) the appetitive properties of cocaine. Rats were surgically implanted with a naltrexone implant (placebo, 10 or 30 mg) and placed into an open field for the recording of social interactions. The naltrexone implants increased latency to initiate contact and decreased pinning, bouts of grooming, and crawl unders on all 7 days. Other rats were surgically implanted with naltrexone (60, 120, or 240 mg) and habituated to a two-chambered conditioned place preference apparatus. After 6 days of conditioning, place preference was computer recorded. Cocaine produced a dose-dependent conditioned place preference in the rats implanted with placebo or 60 mg of naltrexone. The 120 and 240 mg naltrexone implants blocked the emergence of cocaine-induced place preference. The results indicate that naltrexone implants produce significant social behavioral effects within 1 day, and are effective at attenuating the conditioned place preference produced by cocaine.