5-HT1A agonists: alcohol drinking in rats and squirrel monkeys.
BACKGROUND
Increased alcohol intake after administration of low doses of 5-HT(1A )agonists is thought to be due to a reduction in 5-HT impulse flow due to activation of 5-HT(1A) somatodendritic receptors, whereas decreased alcohol drinking found after administration of higher doses of 5-HT(1A) agonists may be mediated by action at postsynaptic 5-HT(1A) receptors.


OBJECTIVE
This study compares Long-Evans rats and squirrel monkeys to examine the hypothesis that low doses of the 5-HT(1A) selective agonists, 8-OH-DPAT and alnespirone, will preferentially increase, and at higher doses decrease alcohol drinking, and whether these effects can be antagonized by WAY 100635.


METHODS
Male Long-Evans rats were induced to drink from two bottles, one containing a solution of 10% ethanol and 1% sucrose (w/v), the other containing an equally preferred concentration of sucrose. Squirrel monkeys also drank from two bottles, one containing a solution of 2% ethanol and 15% sucrose (w/v), the other, water.


RESULTS
In rats, low doses of both 8-OH-DPAT (0.018-0.03 mg/kg) and alnespirone (0.3-3.0 mg/kg) increased alcohol drinking by ca. 100% without altering sucrose intake. The highest dose of 8-OH-DPAT (0.1 mg/kg) suppressed intake of both solutions without significant motor impairment. Pretreatment with WAY 100635 (0.1 mg/kg), shifted the entire dose-effect curve of 8-OH-DPAT to the right, and antagonized the effects of the 0.56 mg/kg dose of alnespirone. In the monkeys, administration of both agonists dose-dependently decreased alcohol intake and were behaviorally sedative.


CONCLUSIONS
These results support the hypothesis that in rats, 5-HT(1A) receptor stimulation activates somatodendritic receptors at lower doses and postsynaptic receptors at higher doses, each with opposite effects on alcohol intake. The absence of such biphasic dose-effect curves in monkeys suggests a different function of 5-HT(1A) somatodendritic receptors in rats and monkeys, at least with regard to alcohol drinking.
McKenzie-Quirk
Sara D
SD
Department of Psychology, Tufts University, 530 Boston Avenue (Bacon Hall), Medford, MA 02155, USA.
Miczek
Klaus A
KA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012453:Saimiri; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013045:Species Specificity; D013141:Spiro Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; C075319:alnespirone; D000431:Ethanol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin