The effect on opioid peptides in the rat brain, after chronic treatment with the anabolic androgenic steroid, nandrolone decanoate.
In recent years, an increase in abuse of anabolic androgenic steroids (AAS) has been seen among individuals not directly connected to sports. Clinical evidence suggests that abuse of these steroids may result in profound changes in personality, expressed by depressive symptoms, irritability and increased aggression. It is still unknown whether these alterations are related to changes in any particular transmitter system or whether they are persistent or reversible. In this study we focused on AAS effect on the endogenous dynorphin and enkephalin system in the brain. Male rats were given intramuscular injections of the AAS nandrolone decanoate (15 mg/kg), once daily for 2 weeks. The levels of the opioid peptide immunoreactivities (ir) were assessed by radioimmunoassay in two groups immediately after the treatment and in two other groups after additional 3 weeks without any drug treatment (recovery period). The result indicates that chronic AAS treatment increased the activity in the dynorphin B- and Met-enkephalin-Arg(6)Phe(7)-ir in the hypothalamus, striatum and periaqueductal gray (PAG) compared to controls. In addition, the steroid induced an imbalance between the dynorphin and the enkephalin opioid system in the nucleus accumbens, hypothalamus and PAG. This imbalance remained after the recovery period. Since increased peptide activity was found in brain regions regulating emotions, dependence, defensive reactions and aggression, it was suggested that the actual endogenous opioid systems are involved in previously reported AAS-induced changes in these behaviours.
Johansson
P
P
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, Sweden. Pia.Johansson@farmbio.uu.se
Hallberg
M
M
Kindlundh
A
A
Nyberg
F
F
D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D009277:Nandrolone / Q000494:pharmacology*; D018847:Opioid Peptides / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists
D045930:Anabolic Agents; D004723:Endorphins; D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004744:Enkephalin, Methionine; D009277:Nandrolone; C027511:enkephalin-Met, Arg(6)-Phe(7)-; D004399:Dynorphins; C036200:rimorphin