Behavioral sensitization to cocaine: cooperation between glucocorticoids and epinephrine.
BACKGROUND
Stressful life experiences facilitate responsiveness to psychostimulant drugs. While there is ample evidence that adrenal glucocorticoids mediate these effects of stress, the role of the sympatho-adrenal system in the effects of psychostimulants is poorly understood.


OBJECTIVE
The present study investigated the role of the two adrenal stress hormones, corticosterone and epinephrine, in sensitization to the locomotor stimulant effects of cocaine.


METHODS
The DBA/2 mouse strain was used, as behavioral sensitization in this strain critically depends on adrenal hormones. Animals were subjected to adrenalectomy ("ADX", surgical removal of the adrenals) or SHAM surgery, and ADX mice were given replacement of epinephrine (5 x 10(-3) mg/kg subcutaneously (s.c.) just prior to each drug administration), corticosterone (20%, s.c., pellet), or both. Mice were subjected to a cocaine sensitization regimen (15.0 mg/kg cocaine on nine consecutive days followed by a 7.5 mg/kg cocaine challenge after a 5-day withdrawal).


RESULTS
In agreement with our previous observations, ADX prevented initiation and expression of cocaine-induced locomotor sensitization. Whereas neither corticosterone nor epinephrine alone were sufficient to reverse the ADX effect, both hormones were necessary to fully restore initiation and retention of sensitization to levels observed in SHAM animals.


CONCLUSIONS
The present findings indicate that corticosterone and epinephrine cooperate to facilitate behavioral responsiveness to cocaine. These data emphasize that in addition to the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system plays a critical role in psychostimulant sensitivity.
de Jong
Inge E M
IE
Medical Pharmacology, Leiden/Amsterdam Center for Drug Research and Leiden University Medical Center, Gorlaeus Laboratories, Einsteinweg 55, P.O. Box 9502, 2300 RA, Leiden, The Netherlands. IDJ@Lundbeck.com
Steenbergen
Peter J
PJ
de Kloet
E Ronald
ER
D000315:Adrenalectomy; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D003345:Corticosterone; D004837:Epinephrine