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Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in the generalization of 5-HT receptor agonists to the ethanol cue in the rat.
Behav Pharmacol. 1998 Jul; 9(4):337-43.BP

Abstract

Although accumulating evidence suggests that serotonergic drugs are able to substitute for the ethanol (EtOH) cue in rats, it is still unclear which 5-HT receptor subtypes are responsible for this phenomenon, and whether these receptors are critically involved in the EtOH cue. In the present study, rats were trained to discriminate EtOH (1000 mg/kg, i.p., t-15 min) from saline in a two-lever food-reinforced procedure, and it was investigated to which extent serotonergic compounds with a certain level of specificity for either 5-HT1B, 5-HT2A or 5-HT2C receptors generalized to the EtOH cue. Subsequently, the involvement of these receptor subtypes was ascertained by the use of selected 5-HT receptor antagonists. The 5-HT1B receptor agonist CP 94,253 (0.3-5 mg/kg, i.p.) and the mixed 5-HT(2C/1B) receptor agonist mCPP (0.1-1 mg/kg, i.p.), but not the preferential 5-HT2A receptor agonist DOI (0.3-1 mg/kg, i.p.), completely generalized to the EtOH cue. Complete generalization of the former two compounds coincided with a decrease in response rate. In antagonism studies, it was shown that the 5-HT1B receptor antagonist GR 127935 (10 mg/kg, i.p.) completely blocked generalization of CP 94,253 to the EtOH cue, suggesting that stimulation of 5-HT1B receptors produces discriminative stimulus effects which are similar to those of EtOH. GR 127935 (10 mg/kg, i.p.), as well as the mixed 5-HT(1B/2C) receptor antagonist metergoline (1 mg/kg, i.p.), and the 5-HT2C receptor antagonist SB 206,553 (1 mg/kg, i.p.) completely blocked generalization of mCPP to the EtOH cue. This suggests that 5-HT1B and 5-HT2C receptors are required for the generalization of mCPP to the EtOH cue. The present findings indicate that activation of 5-HT1B and 5-HT2C, but not of 5-HT2A receptors, mimics the EtOH cue. However, the finding that neither metergoline, nor the 5-HT2A receptor antagonist MDL 100,907 blocked the EtOH cue, suggests that these receptors play only a minor role in the discriminative stimulus effects of a moderately low dose of EtOH.

Authors+Show Affiliations

CNS Research, Bayer AG, Cologne, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10065922

Citation

Maurel, S, et al. "Role of 5-HT1B, 5-HT2A and 5-HT2C Receptors in the Generalization of 5-HT Receptor Agonists to the Ethanol Cue in the Rat." Behavioural Pharmacology, vol. 9, no. 4, 1998, pp. 337-43.
Maurel S, Schreiber R, De Vry J. Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in the generalization of 5-HT receptor agonists to the ethanol cue in the rat. Behav Pharmacol. 1998;9(4):337-43.
Maurel, S., Schreiber, R., & De Vry, J. (1998). Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in the generalization of 5-HT receptor agonists to the ethanol cue in the rat. Behavioural Pharmacology, 9(4), 337-43.
Maurel S, Schreiber R, De Vry J. Role of 5-HT1B, 5-HT2A and 5-HT2C Receptors in the Generalization of 5-HT Receptor Agonists to the Ethanol Cue in the Rat. Behav Pharmacol. 1998;9(4):337-43. PubMed PMID: 10065922.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in the generalization of 5-HT receptor agonists to the ethanol cue in the rat. AU - Maurel,S, AU - Schreiber,R, AU - De Vry,J, PY - 1999/3/5/pubmed PY - 1999/3/5/medline PY - 1999/3/5/entrez SP - 337 EP - 43 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 9 IS - 4 N2 - Although accumulating evidence suggests that serotonergic drugs are able to substitute for the ethanol (EtOH) cue in rats, it is still unclear which 5-HT receptor subtypes are responsible for this phenomenon, and whether these receptors are critically involved in the EtOH cue. In the present study, rats were trained to discriminate EtOH (1000 mg/kg, i.p., t-15 min) from saline in a two-lever food-reinforced procedure, and it was investigated to which extent serotonergic compounds with a certain level of specificity for either 5-HT1B, 5-HT2A or 5-HT2C receptors generalized to the EtOH cue. Subsequently, the involvement of these receptor subtypes was ascertained by the use of selected 5-HT receptor antagonists. The 5-HT1B receptor agonist CP 94,253 (0.3-5 mg/kg, i.p.) and the mixed 5-HT(2C/1B) receptor agonist mCPP (0.1-1 mg/kg, i.p.), but not the preferential 5-HT2A receptor agonist DOI (0.3-1 mg/kg, i.p.), completely generalized to the EtOH cue. Complete generalization of the former two compounds coincided with a decrease in response rate. In antagonism studies, it was shown that the 5-HT1B receptor antagonist GR 127935 (10 mg/kg, i.p.) completely blocked generalization of CP 94,253 to the EtOH cue, suggesting that stimulation of 5-HT1B receptors produces discriminative stimulus effects which are similar to those of EtOH. GR 127935 (10 mg/kg, i.p.), as well as the mixed 5-HT(1B/2C) receptor antagonist metergoline (1 mg/kg, i.p.), and the 5-HT2C receptor antagonist SB 206,553 (1 mg/kg, i.p.) completely blocked generalization of mCPP to the EtOH cue. This suggests that 5-HT1B and 5-HT2C receptors are required for the generalization of mCPP to the EtOH cue. The present findings indicate that activation of 5-HT1B and 5-HT2C, but not of 5-HT2A receptors, mimics the EtOH cue. However, the finding that neither metergoline, nor the 5-HT2A receptor antagonist MDL 100,907 blocked the EtOH cue, suggests that these receptors play only a minor role in the discriminative stimulus effects of a moderately low dose of EtOH. SN - 0955-8810 UR - https://www.unboundmedicine.com/medline/citation/10065922/Role_of_5_HT1B_5_HT2A_and_5_HT2C_receptors_in_the_generalization_of_5_HT_receptor_agonists_to_the_ethanol_cue_in_the_rat_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=10065922.ui DB - PRIME DP - Unbound Medicine ER -