Effects of fluvoxamine on a multiple schedule of ethanol- and food-maintained behavior in two rat strains

Abstract

Rationale: Previous studies show that selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, have a greater effect on ethanol-maintained responding compared with an alternative reinforcer. However, none of these studies matched baseline responding for reinforcers. Because behavioral effects of many drugs depend on the baseline response rate, the preferential effects of SSRIs may be due to different baseline response rates. Objectives: Fluvoxamine effects on ethanol-and foodmaintained responding were compared using a multiple schedule of behavior, providing matched baseline responding and allowing within-subject analysis in two strains of rats. Methods: The multiple schedule consisted of three consecutive 5-min, fixed-ratio five components (Food1, Ethanol, Food2). Fluvoxamine (3-30 mg/kg, i.p.) was administered 30 min presession. In Lewis rats, fluvoxamine effects were determined at several available ethanol concentrations [8, 16, 32, and 8% (w/v) redetermination]. In Sprague-Dawley rats, fluvoxamine effects were determined when the available ethanol concentration was 8% (w/v). Results: Baseline responding was stable and well matched under all conditions except 32% ethanol, when responding for ethanol was lower than for food. After the administration of 17.8 mg/kg fluvoxamine, ethanol-maintained responding was 15-33% lower than food-maintained responding in four of the five conditions tested. Breath ethanol assessments indicated that rats had blood ethanol levels of 33 mg/dl following responding for 8% ethanol. Conclusions: These results are in agreement with previous findings that SSRIs preferentially reduce ethanolmaintained responding and suggest this is not likely due to different baseline levels of responding between the comparison conditions. Further, these results support the hypothesis that alteration of synaptic serotonin can modulate ethanol reinforcement.

Fluvoxamine effects on concurrent ethanol- and food-maintained behaviors.

“…In contrast, in previous studies in which ethanol and food were available under either a multiple schedule or in separate groups, fluvoxamine had the opposite effect, decreasing responding for ethanol to a greater extent or at lower doses than responding for food (Lamb and Järbe, 2001;Ginsburg et al, 2005). The increased resistance to acute fluvoxamine effects on responding for ethanol relative to responding for food suggests that the context in which responding occurs may be an important determinant of the direction and extent of selective treatments effects.…”

“…Further research indicated that fluvoxamine could selectively reduce operant responding maintained by ethanol when compared with responding maintained by food (Lamb and Järbe, 2001). A subsequent within-subjects study replicated this finding in subjects responding for ethanol and food under a multiple fixed-ratio schedule designed to match baseline response rates and experimental histories of subjects (Ginsburg et al, 2005).…”

“…Further research indicated that fluvoxamine could selectively reduce operant responding maintained by ethanol when compared with responding maintained by food (Lamb and Järbe, 2001). A subsequent within-subjects study replicated this finding in subjects responding for ethanol and food under a multiple fixed-ratio schedule designed to match baseline response rates and experimental histories of subjects (Ginsburg et al, 2005).Thus, fluvoxamine appears to preferentially reduce responding for ethanol relative to food, and this effect is not easily explained by differences in subjects' baseline response rates, age, or experimental history.Based on these studies, fluvoxamine would appear to target brain systems preferentially involved in ethanol reinforcement, and could be considered a candidate pharmacotherapy for alcohol abuse or addiction. However, in humans, fluvoxamine is only effective in a subset of alcoholics (Naranjo and Knocke, 2001;Pettinati, 2001).…”

“…This is in contrast to conditions in which food and ethanol are available independently, where ethanol-maintained behavior appears to be more sensitive to decreases following fluvoxamine administration (Lamb and Järbe, 2001;Ginsburg et al 2005). Several hypotheses have been proposed that could account for the inversion of the selective effect of fluvoxamine, including: increased resistance to change due to increased reinforcer frequency, strengthened stimulus control over ethanol-maintained responding, altered demand for food and ethanol, and the impact of fixed-ratio size.…”

“…Previous research from our laboratory demonstrated that fluvoxamine preferentially decreases responding for ethanol relative to food when each is available in isolation or sequentially under a multiple schedule (Lamb and Järbe, 2001;Ginsburg et al, 2005). In the present study, rats were trained to respond on a concurrent fixed-ratio schedule of ethanol and food reinforcement.…”