title: Serotonergic and cholinergic mechanisms during disruption of approach and avoidance behavior.
abstract: Injections of D,L-5-hydroxytryptophan (D,L-5-HTP) into pigeons and rats working on approach schedules produce a period of behavioral depression that is temporally correlated to increased levels of total serotonin (5-?HT) in the telencephalon and diencephalon. Administration of alpha-methyl-meta-tyrosine (alpha-MMT) also results in depressed responding; however, the temporal correlation is with decreased levels of total 5-HT in brain. Our hypothesis to explain these two apparent opposite biochemical states which result in similar behavioral disruptions is that in both cases more 5-HT is released within certain key serotonergic synapses mediating this behavior. Evidence from subcellular studies supports this concept. tnot only are the levels of 5-HT significantly higher in preparations of nerve endings isolated from the telencephalon and diencephalon of pigeons given injections of D,L-5-HTP, but in vitro studies also show that low concentrations of L-5-HTP significantly increased the release of radioactive 5-HT from serotonergic nerve endings. On the other hand, L-5-HTP in much higher concentrations had no effect on the release of labeled dopamine or norephinephrine. A major metabolite of alpha-MMT, alpha-methyl meta tyramine, also caused a significant increase in the release of labeled 5-?HT from similar preparations of nerve endings. Whereas serotonin appears to be involved in the disruption of approach behavior, another series of studies have indicated that acetylcholine may play a role in excitation during avoidance behavior. Behavioral excitation observed following administration of tetrabenazine 18 hr after iproniazid pretreatment to rats working on shock-avoidance schedules was temporally correlated with lowered levels of acetylcholine in the telencephalon. Pretreatment with 0.8 mg/kg of atropine blocked excitation whereas one-eight of this dose increased the duration. Excitation in these rats was shortened by 50% following bilateral septal lesions, which lowered brain acetylcholine levels. Mechanisms to explain these neurochemical correlates of behavior are discussed.
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000502:physiology; D010856:Columbidae; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D007490:Iproniazid / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D008781:Methyltyrosines / Q000378:metabolism / Q000494:pharmacology*; D008959:Models, Neurological; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013045:Species Specificity; D013747:Tetrabenazine / Q000494:pharmacology; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology
chemical_list: D008781:Methyltyrosines; D012701:Serotonin; D001285:Atropine; D006916:5-Hydroxytryptophan; D007490:Iproniazid; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine; D013747:Tetrabenazine