Effects of central and peripheral pretreatment with fluoxetine in gustatory conditioning.

The administration of fluoxetine, a relatively specific serotonin uptake inhibitor, an hour prior to a taste-drug pairing was shown to attenuate the acquisition of taste aversions in a dose-dependent manner. Desipramine which is less effective than fluoxetine in blocking the reuptake of serotonin was also less potent in reducing the magnitude of taste aversions. Depletion of forebrain serotonin by lesions of the dorsal and median raphe nuclei or of norepinephrine by lesions of the dorsal noradrenergic bundle failed to prevent the pretreatment effect produced by either fluoxetine or desipramine. Rats with raphe lesions consistently consumed less of the taste paired with lithium than did control animals; however, this decreased intake occurred under both drug and saline pretreatment conditions, suggesting an increased sensitivity to the taste-lithium pairing rather than a diminution of the pretreatment effect. Rats with dorsal bundle lesions failed to differentiate between drug and saline pretreatment, consuming similar amounts under both conditions. These findings as well as the observation that intraventricular administration of fluoxetine did not produce a pretreatment effect suggest that forebrain serotonergic systems are not the critical site of action for the production of pretreatment effects by monoamine uptake inhibitors. Instead, the hypothesis that the peripheral effects of fluoxetine have a stimulus value that acts by way of an associative mechanism to attenuate gustatory conditioning must be considered.