Abstract
Rationale
The neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) has effects on reward-related behaviors in mice and rats that suggest that it may activate brain reward circuits. Intracranial self-stimulation (ICSS) is an operant behavioral technique that detects changes in the sensitivity of brain reward circuitry following drug administration.
Objective
To examine the effects of the neuroactive steroid allopregnanolone on ICSS and to compare these effects to those of cocaine.
Methods
Male C57BL/6J mice implanted with stimulating electrodes implanted into the medial forebrain bundle responded for reinforcement by electrical stimulation (brain stimulation reward (BSR)). Mice received cocaine (n = 11, 3.0–30.0 mg/kg, intraperitoneal (i.p.)) or the neuroactive steroid allopregnanolone (n = 11, 3.0–17.0 mg/kg, i.p.). BSR thresholds (θ 0) and maximum (MAX) operant response rates after drug treatments were compared to those after vehicle injections.
Results
Cocaine and allopregnanolone dose dependently lowered BSR thresholds relative to vehicle injections. Cocaine was maximally effective (80 % reduction) in the second 15 min following the 30 mg/kg dose, while allopregnanolone was maximally effective (30 % reduction) 15–45 min after the 17 mg/kg dose. Neither drug had significant effects on MAX response rates.
Conclusions
The effects of allopregnanolone on BSR thresholds are consistent with the previously reported effects of benzodiazepines and alcohol, suggesting that positive modulation of GABAA receptors can facilitate reward-related behaviors in C57BL/6J mice.
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Acknowledgment
This work was supported by AA 018335 to CJM, AA016672 to ALM, and T32-AA007573 to the Bowles Center of Alcohol Studies.
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A. Leslie Morrow and C.J. Malanga, senior authors, contributed equally.
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Fish, E.W., Whitman, B.J., DiBerto, J.F. et al. Effects of the neuroactive steroid allopregnanolone on intracranial self-stimulation in C57BL/6J Mice. Psychopharmacology 231, 3415–3423 (2014). https://doi.org/10.1007/s00213-014-3600-8
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DOI: https://doi.org/10.1007/s00213-014-3600-8