Gene - environment interactions determine the individual variability in cocaine self-administration.
Research into factors that determine the propensity to self-administer cocaine has shown that stressors can determine the amount of cocaine self-administered as well as the rate of acquisition. However, the interaction between the genetic make-up of the animal and stress is unknown. This study investigated this interaction by using the genetic animal model consisting of apomorphine susceptible (APO-SUS) and unsusceptible (APO-UNSUS) rats. Animals were allowed to self-administer 0.25 mg/kg cocaine under stressful and habituated conditions. This study revealed that the amount of cocaine consumed was highly dependent on the genetic make-up of the animal as well as the amount of stress during self-administration. Under habituated circumstances the APO-UNSUS rats took far more cocaine than the APO-SUS rats. Under stressful circumstances, however, the APO-SUS rats took far more cocaine than the APO-UNSUS rats. This difference in the amount consumed by APO-SUS and APO-UNSUS rats is likely to be due to the specific neurobiological features of their dopaminergic and, possibly, noradrenergic system as well as the reactivity of their HPA-axis. It is suggested that the amount of a drug consumed and, accordingly, its addictive potential and 'drug-vulnerability' are determined by the interaction between the genetic make-up of the animals and stress, and not by either component alone.
van der Kam
Elizabeth L
EL
Department of Psychoneuropharmacology, Nijmegen Institute of Neuroscience, Radboud University Nijmegen Medical Center, the Netherlands. e.vanderkam@pnf.umcn.nl
Ellenbroek
Bart A
BA
Cools
Alexander R
AR
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004777:Environment; D005796:Genes / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors
D000779:Anesthetics, Local; D018491:Dopamine Agonists; D003042:Cocaine; D001058:Apomorphine