ABSTRACT
BACKGROUND AND PURPOSE: Drugs that more potently or effectively reduce ethanol-maintained behaviour versus an alternative are considered selective and are considered promising pharmacotherapies for alcoholism. Such results are often obtained using separate groups or multiple schedules where ethanol and the alternative are available alone or sequentially. Recently, we observed that when ethanol and food were available sequentially under a multiple schedule, fluvoxamine and varenicline were selective; yet this selectivity disappeared when ethanol and food were concurrently available. EXPERIMENTAL APPROACH: We examined the generality of these findings by comparing doses of several drugs required to decrease ethanol- and food-maintained responding under a multiple schedule and under a concurrent schedule. Effects were determined for chlordiazepoxide, 2,5-dimethoxy-4-iodoamphetamine (DOI), meta-chlorophenylpiperazine (mCPP), morphine, naltrexone and d-amphetamine. KEY RESULTS: Under the multiple schedule, ED50 values for decreases in ethanol-maintained responding were significantly different and lower than ED50 s for decreases in food-maintained responding (demonstrating selectivity) for each drug except for chlordiazepoxide (which was equipotent) and naltrexone (which did not affect responding). However, this selectivity vanished or even inverted under the concurrent schedule, such that ED50 values for decreasing ethanol- and food-maintained responding were not different (or, following DOI, the ED50 for food-maintained responding was lower than for ethanol-maintained responding). CONCLUSIONS AND IMPLICATIONS: Results are consistent with those seen following fluvoxamine and varenicline administration, and suggest that selectivity is assay-dependent. These results indicate the need for careful interpretation of selective drug effects, especially when obtained in situations where ethanol or the alternative is the only programmed reinforcement available.
Subject(s)
Alcoholism/psychology , Eating/psychology , Ethanol/antagonists & inhibitors , Food , Alcoholism/drug therapy , Amphetamines/administration & dosage , Animals , Chlordiazepoxide/administration & dosage , Dextroamphetamine/administration & dosage , Dose-Response Relationship, Drug , Drug Administration Schedule , Eating/drug effects , Ethanol/administration & dosage , Male , Morphinans/administration & dosage , Naltrexone/administration & dosage , Piperazines/administration & dosage , Rats , Rats, Inbred LewABSTRACT
Fluvoxamine, a serotonin reuptake blocker, was previously shown to decrease ethanol-maintained behavior at doses lower than those needed to decrease food-maintained behavior. While these effects could have been due to different response rates and histories of the two groups being compared, a subsequent study found differential effects using a within-subjects design, in which rates of responding were well equated. Another explanation for such differential effects is that food and ethanol reinforcement differ in a quantitative fashion. This is difficult to resolve when comparing between behaviors maintained by different events. To examine how such quantitative differences in reinforcement magnitude might influence the effects of fluvoxamine, we used a multiple schedule of fixed-ratio 30 responding in the pigeon. In each of the three fixed-ratio 30 components, behavior was maintained by a different duration of grain presentation (2, 4, and 8 s). The effects of fluvoxamine and also desipramine were examined. Both dose-dependently decreased fixed-ratio responding. Their effects were independent of the duration of grain presentation maintaining responding. These results do not support the idea that the differential effects of fluvoxamine on ethanol-maintained behavior, as compared with food-maintained behavior, are a result of quantitative differences in reinforcement magnitude.
Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Conditioning, Operant/drug effects , Desipramine/pharmacology , Fluvoxamine/pharmacology , Reinforcement Schedule , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , Columbidae , Dose-Response Relationship, Drug , Food , Reinforcement, PsychologyABSTRACT
Sarcoidosis is rare in young children, and is characterized by skin, joint, and eye changes. Differentiated clinically from juvenile rheumatoid arthritis (JRA) by milder constitutional symptoms and characteristic joint abnormalities, sarcoidosis is confirmed by demonstrating noncaseating granulomas in skin, conjunctival, or synovial biopsies. Recent reports have shown children with features of both sarcoidosis and juvenile rheumatoid arthritis, some with similarly affected family members. We cared for four children with sarcoidosis and severe joint manifestations. Two had a personal or family history of JRA. Three of the four children had ichthyosiform cutaneous manifestations, which may suggest an association between severe joint disease and ichthyosiform changes. Because of the difficulty in making a diagnosis on clinical grounds alone, biopsy of cutaneous lesions is recommended in children with these symptoms.
