Effects of stress modulation on morphine-induced conditioned place preferences and plasma corticosterone levels in Fischer, Lewis, and Sprague-Dawley rat strains.
BACKGROUND
There is a direct relationship between hypothalamic-pituitary-adrenal axis (HPA) reactivity and susceptibility to drug use in outbred rats. Specifically, manipulations that increase or decrease HPA activity also increase or decrease drug intake, respectively. Interestingly, this relationship has not been established in the inbred Fischer (F344) and Lewis (LEW) rat strains that are often used as animal models of susceptibility to drug use.


OBJECTIVE
The present study investigated the effects of manipulations known to affect HPA activity on morphine-induced conditioned place preference (CPP) in male LEW, F344, and Sprague-Dawley (SD) rats.


METHODS
In experiment 1, animals were exposed to an injection of methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and 2-h restraint stress prior to the conditioning of a morphine-induced place preference (1, 4, or 10 mg/kg subcutaneous). In experiment 2, animals were chronically exposed to corticotropin-releasing hormone type 1 receptor antagonist, antalarmin, prior to CPP training. The effects of DMCM/restraint and antalarmin on corticosterone levels were examined in experiments 3 and 4.


RESULTS
In outbred rats, DMCM/restraint increased both HPA activity and morphine-induced CPP, while antalarmin decreased CPP and produced a slight, but nonsignificant, decrease in corticosterone levels. In the inbred rats, however, DMCM/restraint increased plasma corticosterone yet decreased place preferences in the LEW strain, and antalarmin treatment decreased plasma corticosterone but increased place preferences in the F344 strain.


CONCLUSIONS
These data suggest that the relationship between stress and drug use may be nonmonotonic. The use of these inbred strains in genetic analysis of drug addiction may require reexamination.
Grakalic
Ivana
I
Preclinical Pharmacology Section, Behavioral Neuroscience Branch, DHHS/NIH/NIDA Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD, 21224, USA. igrakalic@intra.nida.nih.gov
Schindler
Charles W
CW
Baumann
Michael H
MH
Rice
Kenner C
KC
Riley
Anthony L
AL
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013312:Stress, Physiological / Q000150:complications*
D009020:Morphine; D003345:Corticosterone