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

Abstract 

Rationale: Previously, we have shown that increasing 5-hydroxytryptamine (5-HT) activity attenuates responding for conditioned reward (CR), and the response potentiating effect of d-amphetamine on this behaviour. Objectives: The present experiments examined the effects of reducing 5-HT function on responding for CR. Methods: In experiment 1, thirsty rats were trained to associate a CS+ with water delivery. The neurotoxin 5,7-DHT was then injected into the dorsal and median raphe nuclei. Subsequently, rats were treated with intra-accumbens d-amphetamine (1, 3, 10 µg) or saline and given access to two levers. One lever delivered the CS+ (now termed a CR), while the other was inactive. In experiment 2, the lesion was carried out prior to conditioning, and approach behaviour to the water magazine was measured during CS+ periods. Subsequently, rats were allowed to respond for the CS. In experiment 3, non-deprived rats learned to associate a CS+ with 10% sucrose; these animals also experienced a CS– which was not paired with sucrose. During 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 hippocampus. In experiment 1, responding for the CR was enhanced by both d-amphetamine and 5-HT depletion in an additive fashion. In experiments 2 and 3, the discriminative control over behaviour exerted by the CS+ was not affected by 5-HT depletion. However, compared to control animals 5-HT-depleted rats showed higher levels of operant responding for the CR. Conclusions: Serotonin depletion selectively enhances responding for CR. Although 5-HT depletion did not potentiate the effects of d-amphetamine, it is suggested that CRs activate the mesolimbic dopamine system, and that removal of an inhibitory influence of 5-HT on the activity of this system results in increased responding for CR in 5,7-DHT-treated rats.