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Effects of long term haloperidol treatment and its withdrawal on ketamine-induced linguopharyngeal events in rats: A dyskinesia model
147 METHODOLOGICAL ISSUES IN THE PET SCAN EVALUAI’lON OF F-18 NMS BINDING IN TARDIVE DYSKINESIA (TD) Miklos F. Losonczy, Michael Davidson, Daniel tobel. Alfred P. Wolf, Kenneth L. Davis Bronx, NY In order to examine the hypothesis that dopamine receptor proliferation is present in TD, a PET study of RDC + chronic schizophrenics with and without TD is in progress. F-18 N-methylspiroperidol (NMS) binding in the striatum has been determined for eight subjects with moderate TD, as assessed by the AIMS, compared to six subjects without TD. All subjects were male and matched as much as practical for age, length of illness, neuroleptic exposure and severity of psychotic symptoms, and were neuroleptic-free at least four weeks. Dopamine receptor concentrations were presumed to be proportional to the slope of the Patlak curve for the rate of uptake of NMS and were 35% higher in the subjects without TD than in the subjects with TD (2-tailed p < .05), implying a hyposensitivity of dopamine receptors in the TD group. However, height and weight were significantly negatively correlated with dopamine receptor concentration in the overall sample and both were higher in the TD group. This confounds simple interpretation of group differences in dopamine receptor densities and underscores the need for careful analyses and matching for a wide range of factors in studies of dopamine receptors by PET.
148 EFFECTS OF LONG TERM HALOPERIDOL TREATMENT AND ITS WITHDRAWAL ON KETAMINE-INDUCED LINGUOPHARYNGEAL EVENTS IN RATS: A DYSKINESIA MODEL L. Marco, R. Joshi, C. Brown Mobile, AL We recorded ketamine-induced linguopharyngeal events (KILPE) in rats before long term haloperidol, during, and after its withdrawal. Results were compared to baseline values and to a control group without neuroleptic (NL). Rats were anesthetized with ketamine hydrochloride i.m. (100 mg/kg) for all three stages, and mounted on a stereotaxic frame. KILPE were monitored by tying the tongue tip to a force displacement transducer fed to a polygraph. Baseline recording was done before NL treatment, again after three months of treatment, a third 48 hours after NL withdrawal and two more eight and 20 days later. We also took counts of linguopharyngeal events (LPE) in a Broome type restrainer during all stages of NL. There was an increase over time in the level of KILPE seen in both control and experimental rats. No differences between control and NL-treated rats were observed. In Broome, there was an increase in LPE, more marked in the NL-treated rats as treatment proceeded in time. Repeated injections of ketamine also had cumulative effects on LPE. These results demonstrate close interaction between NL and ketamine in generating dyskinetic activity and further suggest that ketamine is a good model not only for acute but also for tardive dyskinesia.
148 EFFECTS OF LONG TERM HALOPERIDOL TREATMENT AND ITS WITHDRAWAL ON KETAMINE-INDUCED LINGUOPHARYNGEAL EVENTS IN RATS: A DYSKINESIA MODEL L. Marco, R. Joshi, C. Brown Mobile, AL We recorded ketamine-induced linguopharyngeal events (KILPE) in rats before long term haloperidol, during, and after its withdrawal. Results were compared to baseline values and to a control group without neuroleptic (NL). Rats were anesthetized with ketamine hydrochloride i.m. (100 mg/kg) for all three stages, and mounted on a stereotaxic frame. KILPE were monitored by tying the tongue tip to a force displacement transducer fed to a polygraph. Baseline recording was done before NL treatment, again after three months of treatment, a third 48 hours after NL withdrawal and two more eight and 20 days later. We also took counts of linguopharyngeal events (LPE) in a Broome type restrainer during all stages of NL. There was an increase over time in the level of KILPE seen in both control and experimental rats. No differences between control and NL-treated rats were observed. In Broome, there was an increase in LPE, more marked in the NL-treated rats as treatment proceeded in time. Repeated injections of ketamine also had cumulative effects on LPE. These results demonstrate close interaction between NL and ketamine in generating dyskinetic activity and further suggest that ketamine is a good model not only for acute but also for tardive dyskinesia.