Selective destruction of brain serotonin neurons by 5,7-dihydroxytryptamine increases responding for a conditioned reward

Rationale: Previously, we have shown that increasing 5-hydroxytryptamine (5 -HT) activity attenuates responding for conditioned reward (CR), and the re sponse potentiating effect of d-amphetamine on this behaviour. Objectives: The present experiments examined the effects of reducing 5-HT function on r esponding for CR. Methods: In experiment 1, thirsty rats were trained to as sociate a CS+ with water delivery. The neurotoxin 5,7-DHT was then injected into the dorsal and median raphe nuclei. Subsequently, rats were treated w ith intraaccumbens d-amphetamine (1, 3, 10 mu g) or saline and given access to two levers. One lever delivered the CS+ (now termed a CR), while the ot her was inactive. In experiment 2, the lesion was carried out prior to cond itioning, and approach behaviour to the water magazine was measured during CS+ periods. Subsequently, rats were allowed to respond for the CS. In expe riment 3, non-deprived rats learned to associate a CS+ with 10% sucrose; th ese animals also experienced a CS- which was not paired with sucrose. Durin g a test phase responses on the two levers delivered either the CS+ or the CS-. Results, 5,7-DHT substantially reduced 5-HT levels in striatum and hip pocampus. In experiment 1, responding for the CR was enhanced by both d-amp hetamine and 5-HT depletion in an additive fashion. In experiments 2 and 3, the discriminative control over behaviour exerted by the CS+ was not affec ted by 5-HT depletion. However, compared to control animals 5-HT-depleted r ats showed higher levels of operant responding for the CR. Conclusions: Ser otonin depletion selectively enhances responding for CR. Although 5-HT depl etion did not potentiate the effects of d-amphetamine, it is suggested that CRs activate the mesolimbic dopamine system, and that removal of an inhibi tory influence of 5-HT on the activity of this system results in increased responding for CR in 5,7-DHT-treated rats.