title: Selective destruction of brain serotonin neurons by 5,7-dihydroxytryptamine increases responding for a conditioned reward.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 intraaccumbens d-amphetamine (1, 3, 10 micrograms) 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.
authors.affiliation: Department of Psychiatry, University of Toronto, Ontario, Canada. fletcher@psych.toronto.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Fletcher
authors.forename: K M
authors.initials: KM
authors.lastname: Korth
authors.forename: J W
authors.initials: JW
authors.lastname: Chambers
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine