Abstract
The GABA(A)-receptor agonist neuroactive steroid 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) has anxiolytic and locomotor stimulant effects and shares some subjective properties with benzodiazepines. Barbiturates and ethanol, but there have been no studies of its reinforcing or rewarding effects. The present study examined the rewarding properties of 3α,5α-P using the conditioned place preference paradigm. Male DBA/2J mice received four pairings of a distinctive floor stimulus with 3α,5α-P (3.2, 10 or 17 mg/kg, IP) in an unbiased conditioning procedure. On alternate days a different distinctive floor was paired with vehicle. At the lowest dose (3.2 mg/kg), there was no difference between conditioning subgroups in preference for the drug-paired floor type, indicating an absence of place conditioning. However, a dose-dependent conditioned preference was evident at the higher doses as shown by the greater amount of time spent on the floor paired with 3α,5α-P. In addition, 3α,5α-P produced a dose-dependent increase in locomotor activity, which was significant following the 17 mg/kg dose. A control study showed no effect of the β-cyclodextrin vehicle on place conditioning in the absence of neurosteroid. These results provide the first demonstration that 3α,5α-P, an endogenous modulator of GABA(A) receptor function, possesses rewarding properties using the conditioned place preference paradigm.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 261-264 |
| Number of pages | 4 |
| Journal | Pharmacology Biochemistry and Behavior |
| Volume | 56 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1997 |
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Keywords
- conditioned place preference
- GABA(A)-receptor agonist
- inbred mice
- locomotor activity
- neuroactive steroid
- reward
ASJC Scopus subject areas
- Biochemistry
- Behavioral Neuroscience
- Pharmacology
Cite this
Rewarding effect of the neuroactive steroid 3α-hydroxy-5α-pregnan-20-one in mice. / Finn, Deborah (Deb); Phillips, Tamara; Okorn, Dobrina M.; Chester, Julia A.; Cunningham, Christopher.
In: Pharmacology Biochemistry and Behavior, Vol. 56, No. 2, 02.1997, p. 261-264.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Rewarding effect of the neuroactive steroid 3α-hydroxy-5α-pregnan-20-one in mice
AU - Finn, Deborah (Deb)
AU - Phillips, Tamara
AU - Okorn, Dobrina M.
AU - Chester, Julia A.
AU - Cunningham, Christopher
PY - 1997/2
Y1 - 1997/2
N2 - The GABA(A)-receptor agonist neuroactive steroid 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) has anxiolytic and locomotor stimulant effects and shares some subjective properties with benzodiazepines. Barbiturates and ethanol, but there have been no studies of its reinforcing or rewarding effects. The present study examined the rewarding properties of 3α,5α-P using the conditioned place preference paradigm. Male DBA/2J mice received four pairings of a distinctive floor stimulus with 3α,5α-P (3.2, 10 or 17 mg/kg, IP) in an unbiased conditioning procedure. On alternate days a different distinctive floor was paired with vehicle. At the lowest dose (3.2 mg/kg), there was no difference between conditioning subgroups in preference for the drug-paired floor type, indicating an absence of place conditioning. However, a dose-dependent conditioned preference was evident at the higher doses as shown by the greater amount of time spent on the floor paired with 3α,5α-P. In addition, 3α,5α-P produced a dose-dependent increase in locomotor activity, which was significant following the 17 mg/kg dose. A control study showed no effect of the β-cyclodextrin vehicle on place conditioning in the absence of neurosteroid. These results provide the first demonstration that 3α,5α-P, an endogenous modulator of GABA(A) receptor function, possesses rewarding properties using the conditioned place preference paradigm.
AB - The GABA(A)-receptor agonist neuroactive steroid 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) has anxiolytic and locomotor stimulant effects and shares some subjective properties with benzodiazepines. Barbiturates and ethanol, but there have been no studies of its reinforcing or rewarding effects. The present study examined the rewarding properties of 3α,5α-P using the conditioned place preference paradigm. Male DBA/2J mice received four pairings of a distinctive floor stimulus with 3α,5α-P (3.2, 10 or 17 mg/kg, IP) in an unbiased conditioning procedure. On alternate days a different distinctive floor was paired with vehicle. At the lowest dose (3.2 mg/kg), there was no difference between conditioning subgroups in preference for the drug-paired floor type, indicating an absence of place conditioning. However, a dose-dependent conditioned preference was evident at the higher doses as shown by the greater amount of time spent on the floor paired with 3α,5α-P. In addition, 3α,5α-P produced a dose-dependent increase in locomotor activity, which was significant following the 17 mg/kg dose. A control study showed no effect of the β-cyclodextrin vehicle on place conditioning in the absence of neurosteroid. These results provide the first demonstration that 3α,5α-P, an endogenous modulator of GABA(A) receptor function, possesses rewarding properties using the conditioned place preference paradigm.
KW - conditioned place preference
KW - GABA(A)-receptor agonist
KW - inbred mice
KW - locomotor activity
KW - neuroactive steroid
KW - reward
UR - http://www.scopus.com/inward/record.url?scp=0031043365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031043365&partnerID=8YFLogxK
U2 - 10.1016/S0091-3057(96)00218-3
DO - 10.1016/S0091-3057(96)00218-3
M3 - Article
VL - 56
SP - 261
EP - 264
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 2
ER -