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Psychopharmacology (Berl). 2014 Sep;231(17):3415-23. doi: 10.1007/s00213-014-3600-8. Epub 2014 May 9.

Effects of the neuroactive steroid allopregnanolone on intracranial self-stimulation in C57BL/6J mice.

Author information

1
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB# 7178, 104 Manning Dr., Chapel Hill, NC, 27599, USA, efish@med.unc.edu.

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.

PMID:
24810108
PMCID:
PMC4692244
DOI:
10.1007/s00213-014-3600-8
[Indexed for MEDLINE]
Free PMC Article
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