title: Adolescents are more vulnerable to cocaine addiction: behavioral and electrophysiological evidence.
abstract: In humans, adolescence is a period of heightened propensity to develop cocaine addiction. It is unknown whether this is attributable to greater access and exposure to cocaine at this age, or whether the adolescent brain is particularly vulnerable to the addictive properties of cocaine. Here, we subjected male adolescent (P42) and adult (∼P88) rats to a wide range of cocaine self-administration procedures. In addition, to determine whether behavioral differences are associated with developmental differences in dopaminergic activity, we examined and manipulated the activity of dopamine neurons. Relative to adults, adolescent rats took cocaine more readily, were more sensitive to lower doses, showed greater escalation of cocaine intake, and were less susceptible to increases in price (i.e., were more "inelastic"). In parallel, adolescents also showed elevated activity of ventral tegmental area dopamine neurons, a feature known to be associated with increased self-administration behavior. Pharmacological manipulation of dopamine D2 receptor function with quinpirole (agonist) or eticlopride (antagonist), to alter dopamine neuron activity, eliminated age differences in cocaine self-administration. These data suggest a causal relationship between behavioral and electrophysiological determinants of cocaine addiction liability. In conclusion, adolescents show behavioral and electrophysiological traits of heightened addiction liability.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, Illinois 60064, USA.
authors.forename: Wai Chong
authors.initials: WC
authors.lastname: Wong
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Ford
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Pagels
authors.forename: James E
authors.initials: JE
authors.lastname: McCutcheon
authors.forename: Michela
authors.initials: M
authors.lastname: Marinelli
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000375:Aging / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012457:Salicylamides / Q000494:pharmacology; D012646:Self Administration; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000166:cytology
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D012457:Salicylamides; D019257:Quinpirole; C005618:benzoylecgonine; D003042:Cocaine; C045989:eticlopride; C034524:ecgonine methyl ester