title: Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD).
abstract: BACKGROUND
  After decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however.
  
  
  OBJECTIVE
  Two commonly studied hallucinogens, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and in vitro to determine the pharmacology of their behavioral effects in an animal model.
  
  
  METHODS
  Rabbits were administered DOI or LSD and observed for head bob behavior after chronic drug treatment or after pretreatment with antagonist ligands. The receptor binding characteristics of DOI and LSD were studied in vitro in frontocortical homogenates from naïve rabbits or ex vivo in animals receiving an acute drug injection.
  
  
  RESULTS
  Both DOI- and LSD-elicited head bobs required serotonin(2A) (5-HT(2A)) and dopamine(1) (D(1)) receptor activation. Serotonin(2B/2C) receptors were not implicated in these behaviors. In vitro studies demonstrated that LSD and the 5-HT(2A/2C) receptor antagonist, ritanserin, bound frontocortical 5-HT(2A) receptors in a pseudo-irreversible manner. In contrast, DOI and the 5-HT(2A/2C) receptor antagonist, ketanserin, bound reversibly. These binding properties were reflected in ex vivo binding studies. The two hallucinogens also differed in that LSD showed modest D(1) receptor binding affinity whereas DOI had negligible binding affinity at this receptor.
  
  
  CONCLUSIONS
  Although DOI and LSD differed in their receptor binding properties, activation of 5-HT(2A) and D(1) receptors was a common mechanism for eliciting head bob behavior. These findings implicate these two receptors in the mechanism of action of hallucinogens.
authors.affiliation: Drexel University College of Medicine, Department of Pharmacology & Physiology, 245 N. 15th Street, MS488, Philadelphia, PA, 19102, United States. eman227@gmail.com
authors.forename: Emmanuelle A D
authors.initials: EA
authors.lastname: Schindler
authors.forename: Kuldip D
authors.initials: KD
authors.lastname: Dave
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Smolock
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Aloyo
authors.forename: John A
authors.initials: JA
authors.lastname: Harvey
mesh_terms: D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006213:Hallucinogens / Q000494:pharmacology*; D007650:Ketanserin / Q000378:metabolism / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D016713:Ritanserin / Q000378:metabolism / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D013696:Temperature
chemical_list: D000662:Amphetamines; D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D017447:Receptors, Dopamine D1; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine