Blockade of androgen or estrogen receptors reduces nandrolone's ability to modulate acute reward-related neurochemical effects of amphetamine in rat brain.
Previously we have reported that sub-chronic administration of nandrolone modifies reward-related neurochemical effects of psychomotor stimulant drugs of abuse. The aim of the present study was to evaluate whether the ability of nandrolone (19-nortestosterone) to attenuate the effects of amphetamine depends on activation of androgen (AR) or estrogen receptors (ER). We used an in vivo microdialysis technique in fully conscious rats to monitor whether administration of the AR-antagonist flutamide (7x50 mg/kg) or the ER-antagonist clomiphene (7x20 mg/kg), attenuates nandrolone-induced modulation of dopaminergic and serotonergic effects of acute injections of amphetamine (1 mg/kg). Dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured from the samples using high performance liquid chromatography (HPLC). Blocking the androgen receptors with flutamide abolished the attenuating effect of nandrolone pre-treatment on amphetamine-induced elevation of extracellular DA concentration. Blocking the estrogen receptors with clomiphene did the same but to a lesser extent. In conclusion, the results of this study show that the ability of nandrolone to attenuate the effects of amphetamine depends on activation of androgen receptors or to a lesser extent, on estrogen receptors.
Kurling-Kailanto
Sanna
S
Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, Helsinki, Finland. sanna.kailanto@thl.fi
Kankaanpää
Aino
A
Hautaniemi
Janne
J
Seppälä
Timo
T
D018663:Adrenergic Agents / Q000494:pharmacology; D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D045930:Anabolic Agents / Q000494:pharmacology; D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000494:pharmacology; D008297:Male; D009277:Nandrolone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D012201:Reward; D013997:Time Factors
D018663:Adrenergic Agents; D045930:Anabolic Agents; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000697:Central Nervous System Stimulants; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D009277:Nandrolone; D000661:Amphetamine