Abstract
A drug discrimination procedure was used to characterize the ethanol-like effects of a variety of 5-HT1 agonists. Previous studies found that the degree of substitution of the 5-HT(1B/2C) agonist TFMPP (m-trifluoromethylphenylpiperazine) depended on the training dose of ethanol. The present studies extend this initial finding to four additional 5-HT agonists with different selectivity for 5-HT(1A), 5-HT(1B), or 5-HT(2C) receptors: CGS 12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate), mCPP [1-(3-chlorophenyl)piperazine diHCl], RU 24969 [5-methoxy-3(1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole succinate and 8-OH DPAT [±)-8-hydroxy-2-(di-n-propylamino)tetralin HBr]. Separate groups of rats were trained to discriminate 1.0 g/kg (n=7), 1.5 g/kg (n=6) or 2.0 g/kg (n=8) ethanol from water. Following training, three to five doses of each 5-HT agonists were tested twice in each rat. The most selective 5-HT(1B) agonist tested, CGS 12066B (3-17 mg/kg; IP), completely substituted for the 1.0 g/kg ethanol, but not for 1.5 or 2.0 g/kg ethanol. Likewise, the 5-HT(1B/2C) agonist mCPP (0.56-1.7 mg/kg; IP) completely substituted only in the 1.0 g/kg ethanol training group. The 5-HT(1A/1B) agonist RU 24969 (0.1-3.0 mg/kg; IP) substituted for all training doses of ethanol, although in a lower proportion of the rats tested in the 2.0 g/kg ethanol training group. Finally, the 5-HT(1A) agonist 8-OH DPAT (0.1-1.0 mg/kg; IP) did not substitute completely for any ethanol training dose. The results consistently show that agonists with 5-HT(1B) activity produce discriminative stimulus effects similar to low and intermediate, but not high, ethanol training doses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 133-141 |
| Number of pages | 9 |
| Journal | Psychopharmacology |
| Volume | 133 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1997 |
| Externally published | Yes |
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Keywords
- 5-HT
- 8-OH DPAT
- Alcohol
- CGS 12066B
- Ethanol
- mCPP
- Rats discrimination
- RU 24969
- TFMPP
ASJC Scopus subject areas
- Pharmacology
Cite this
Characterization of the ethanol-like discriminative stimulus effects of 5-HT receptor agonists as a function of ethanol training dose. / Grant, Kathleen (Kathy); Colombo, Giancarlo; Gatto, Gregory J.
In: Psychopharmacology, Vol. 133, No. 2, 1997, p. 133-141.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of the ethanol-like discriminative stimulus effects of 5-HT receptor agonists as a function of ethanol training dose
AU - Grant, Kathleen (Kathy)
AU - Colombo, Giancarlo
AU - Gatto, Gregory J.
PY - 1997
Y1 - 1997
N2 - A drug discrimination procedure was used to characterize the ethanol-like effects of a variety of 5-HT1 agonists. Previous studies found that the degree of substitution of the 5-HT(1B/2C) agonist TFMPP (m-trifluoromethylphenylpiperazine) depended on the training dose of ethanol. The present studies extend this initial finding to four additional 5-HT agonists with different selectivity for 5-HT(1A), 5-HT(1B), or 5-HT(2C) receptors: CGS 12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate), mCPP [1-(3-chlorophenyl)piperazine diHCl], RU 24969 [5-methoxy-3(1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole succinate and 8-OH DPAT [±)-8-hydroxy-2-(di-n-propylamino)tetralin HBr]. Separate groups of rats were trained to discriminate 1.0 g/kg (n=7), 1.5 g/kg (n=6) or 2.0 g/kg (n=8) ethanol from water. Following training, three to five doses of each 5-HT agonists were tested twice in each rat. The most selective 5-HT(1B) agonist tested, CGS 12066B (3-17 mg/kg; IP), completely substituted for the 1.0 g/kg ethanol, but not for 1.5 or 2.0 g/kg ethanol. Likewise, the 5-HT(1B/2C) agonist mCPP (0.56-1.7 mg/kg; IP) completely substituted only in the 1.0 g/kg ethanol training group. The 5-HT(1A/1B) agonist RU 24969 (0.1-3.0 mg/kg; IP) substituted for all training doses of ethanol, although in a lower proportion of the rats tested in the 2.0 g/kg ethanol training group. Finally, the 5-HT(1A) agonist 8-OH DPAT (0.1-1.0 mg/kg; IP) did not substitute completely for any ethanol training dose. The results consistently show that agonists with 5-HT(1B) activity produce discriminative stimulus effects similar to low and intermediate, but not high, ethanol training doses.
AB - A drug discrimination procedure was used to characterize the ethanol-like effects of a variety of 5-HT1 agonists. Previous studies found that the degree of substitution of the 5-HT(1B/2C) agonist TFMPP (m-trifluoromethylphenylpiperazine) depended on the training dose of ethanol. The present studies extend this initial finding to four additional 5-HT agonists with different selectivity for 5-HT(1A), 5-HT(1B), or 5-HT(2C) receptors: CGS 12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate), mCPP [1-(3-chlorophenyl)piperazine diHCl], RU 24969 [5-methoxy-3(1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole succinate and 8-OH DPAT [±)-8-hydroxy-2-(di-n-propylamino)tetralin HBr]. Separate groups of rats were trained to discriminate 1.0 g/kg (n=7), 1.5 g/kg (n=6) or 2.0 g/kg (n=8) ethanol from water. Following training, three to five doses of each 5-HT agonists were tested twice in each rat. The most selective 5-HT(1B) agonist tested, CGS 12066B (3-17 mg/kg; IP), completely substituted for the 1.0 g/kg ethanol, but not for 1.5 or 2.0 g/kg ethanol. Likewise, the 5-HT(1B/2C) agonist mCPP (0.56-1.7 mg/kg; IP) completely substituted only in the 1.0 g/kg ethanol training group. The 5-HT(1A/1B) agonist RU 24969 (0.1-3.0 mg/kg; IP) substituted for all training doses of ethanol, although in a lower proportion of the rats tested in the 2.0 g/kg ethanol training group. Finally, the 5-HT(1A) agonist 8-OH DPAT (0.1-1.0 mg/kg; IP) did not substitute completely for any ethanol training dose. The results consistently show that agonists with 5-HT(1B) activity produce discriminative stimulus effects similar to low and intermediate, but not high, ethanol training doses.
KW - 5-HT
KW - 8-OH DPAT
KW - Alcohol
KW - CGS 12066B
KW - Ethanol
KW - mCPP
KW - Rats discrimination
KW - RU 24969
KW - TFMPP
UR - http://www.scopus.com/inward/record.url?scp=0030767205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030767205&partnerID=8YFLogxK
U2 - 10.1007/s002130050383
DO - 10.1007/s002130050383
M3 - Article
C2 - 9342779
AN - SCOPUS:0030767205
VL - 133
SP - 133
EP - 141
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 2
ER -