Brief exposure of mice to 60 Hz magnetic fields reduces the analgesic effects of the neuroactive steroid, 3a-hydroxy-4-pregnen-20-one M. Kavaliers a,b,c, *, J.P. Wiebe b,d , K.-P. Ossenkopp a,b,c a Department of Psychology, Social Sciences Centre, University of Western Ontario, London, Ontario N6A 5C2, Canada b Neuroscience Program, University of Western Ontario, London, Ontario N6A 5C2, Canada c Biolectromagnetics Western, University of Western Ontario, London, Ontario N6A 5C2, Canada d Department of Zoology, University of Western Ontario, London, Ontario N6A 5B7, Canada Received 21 August 1998; received in revised form 12 October 1998; accepted 12 October 1998 Abstract Relatively weak, extremely low frequency (ELF), magnetic fields have been shown to exert a variety of biological effects, although the modes of action remain to be established. Neuroactive steroids and neurosteroids have been shown to produce a diverse range of rapid centrally mediated behavioral and physiological effects that are reported to be sensitive to magnetic fields. Here we show that brief exposure of male mice to an ELF magnetic field (30 min, 60 Hz, 141 mT peak) significantly reduces the analgesic effects arising from intracerebroventricular (i.c.v.) administration of the centrally produced allylic neuroactive steroid, 3a-hydroxy-4-pregnen-20-one (3aHP) and that the dihydropyridine (DHP) calcium channel antagonists, diltiazem and nifedipine, block the inhibitory effects of the 60 Hz ELF on 3aHP-induced analgesia. These results indicate that exposure to 60 Hz ELF affects the analgesic effects of neuroactive steroids such as 3aHP through alterations in calcium channel function. These findings raise the possibility that ELF magnetic fields may, in part, exert their actions through effects on diverse neuroactive steroid modulated processes.  1998 Elsevier Science Ireland Ltd. All rights reserved Keywords: Analgesia; Neuroactive steroids; 60 Hz; Extremely low frequency magnetic field; Calcium channel A number of magnetic field exposures, such as 60 Hz ELF fields, have been shown to reduce exogenous opiate and endogenous opioid peptide-mediated antinociception (‘analgesia’) in a variety of species, including humans [9,10,15,20]. Evidence suggests that the mechanisms of action of the ELF magnetic fields involve alterations in Ca 2+ flux, the functioning of calcium channels, Ca 2+ -acti- vated and diacylglycerol/phospolipid-dependent protein kinase (protein kinase C; PKC), nitric oxide (NO) produc- tion and NO synthase activity [1,9,12,14]. These effects on cell signaling pathways suggest that ELF magnetic fields may also influence other neuromodulation systems. Results of recent research have implicated non- genomically acting neuroactive steroids and neurosteroids in the rapid modulation of diverse physiological and beha- vioral processes [15,19] that are reported to be sensitive to ELF magnetic fields. In particular, two naturally occurring specific 5a-reduced metabolites of progesterone, 3a- hydroxy-5a-pregnan-20-one (allopregnanolone) and 5a- pregnane-3a,21-diol-20-one (3a,5a-tetrahydeoxycorticos- terone, 5a-THDOC) have been shown to produce rapid centrally mediated non-genomic effects on arousal, CNS excitability, feeding, aggression, sociosexual behavior, mood and anxiety, and the modulation of pain sensitivity [3,5–7,11,16,18,22]. Although attention has primarily focused on the afore- mentioned 5a-reduced metabolites, there is evidence that the centrally synthesized 3a-hydroxy-delta-4 allylic neuro- steroid, 3a-hydroxy-4-pregnen-20-one (3aHP) also has Neuroscience Letters 257 (1998) 155–158 0304-3940/98/$ - see front matter  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00835-0 * Corresponding author. Tel.: +1 519 6792111, ext.: 6084; fax: +1 519 6613961; e-mail: kavalier@julian.uwo.ca