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Selective Inhibition of Alcohol Intake in Diverse Alcohol‐Preferring Rat Strains by the 5‐HT 2A Antagonists Amperozide and FG 5974
Author(s) -
Overstreet David H.,
McArthur Robert A.,
Rezvani Amir H.,
Post Claes
Publication year - 1997
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1997.tb04475.x
Subject(s) - saccharin , alcohol , chemistry , antagonism , self administration , antagonist , pharmacology , agonist , ethanol , receptor , 5 ht receptor , receptor antagonist , endocrinology , medicine , serotonin , biochemistry
The present studies sought to elucidate the role of 5‐HT 2A receptor antagonists in suppressing alcohol intake by comparing the effects of amperozide and FG 5974 on alcohol, food, and water intake in strains of alcohol‐preferring rats: P, Alko Alcohol (AA), and Fawn‐Hooded (FH). Both amperozide and FG 5974 have 5‐HT 2A receptor antagonist properties, but FG 5974 also shows presynaptic 5‐HT 1A receptor agonist activity. After establishment of stable baselines for intake measures in a two‐bottle continuous access paradigm, rats ( n = 10) were injected with 1 of 5 doses (0, 1.0, 2.5, 5.0, and 10.0 mg/kg, sc) of amperozide or FG 5974 at weekly intervals. Amperozide dose‐dependently reduced alcohol intake, total fluid intake, and alcohol preference in all three strains under continuous access conditions, whereas FG 5974 was less effective. Food intake was also suppressed by amperozide at higher doses, whereas it was increased by FG 5974. Amperozide also dose‐dependently reduced alcohol intake when it was available for only 1 hr/day, but FG 5974 tended to increase it. After oral administration, amperozide was also more effective than FG 5974 in reducing alcohol intake. Despite these differences in efficacy in suppressing alcohol intake, both compounds produced taste aversion to a novel saccharin solution. These complex findings suggest that biochemical properties other than 5‐HT 2A receptor antagonism (e.g., 5‐HT 1A receptor agonism) may be involved in the effects of amperozide and FG 5974 on alcohol intake and other consummatory behaviors.