The effect of the selective 5-HT 3 receptor antagonist MDL 72222 on voluntary ethanol consumption was examined in Sardinian ethanol-preferring (SP) rats in a free choice (10% ethanol and water) experiment. SP rats consumed 8.1 ± 1.1 g/kg ethanol daily. MDL 72222 treatment (3.0, 5.0 and 7.0 mg/kg i.p. 3 times daily for 6 days) inhibited ethanol consumption during the 6 days of treatment by 25%, 50% and 75%, respectively, without modifying total fluid intake. We suggest that 5-HT 3 receptor activation plays a permissive role in alcohol preference.
The aim of this study was to evaluate whether the number of women recruited for studies to establish the efficacy of medications approved for treatment of alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to reveal possible gender differences in the response to these medications and in suggesting the use of different doses in female patients. Our results show that the rates of women recruited for studies evaluating the efficacy of disulfiram (1%), benzodiazepines (3%), and anticonvulsants (13%) were too low to establish possible gender differences. The rates of women recruited for studies evaluating the efficacy of acamprosate (22%), naltrexone (23%), and nalmefene (30%) were higher and allowed evaluation of data obtained for female patients. Women receive medications for treatment of AD and/or AWS for which efficacy has been demonstrated in studies in which men were more largely represented.
ABSTRACT Sardinian alcohol‐preferring (sP) and ‐non‐preferring (sNP) rats are one of the pairs of rat lines selectively bred for high and low alcohol preference and consumption, respectively, under the homecage, continuous two‐bottle choice regimen. sP rats meet most of the fundamental criteria for an animal model of alcoholism, in that they voluntarily consume sufficient amounts of alcohol to achieve significant blood alcohol levels and produce psychopharmacological effects, including anxiolysis and motor stimulation. sP rats are also willing to ‘work’ (such as lever‐pressing) for alcohol. Chronic alcohol drinking in sP rats results in the development of tolerance to a given effect of alcohol (specifically, motor incoordination) and relapse‐like drinking (the alcohol deprivation effect). Conversely, sNP rats avoid alcohol virtually completely; their avoidance for alcohol being resistant even to an environmental manipulation such as long‐term exposure to alcohol plus sucrose. sP and sNP rats have been characterized for different phenotypes, possibly associated to their different alcohol preference and consumption. In comparison with sNP rats, alcohol‐naive sP rats displayed (1) more anxiety‐related behaviors; (2) higher initial sensitivity to the locomotor stimulating and sedative/hypnotic effects of alcohol; and (3) lower sensitivity to the aversive effects of alcohol. The present paper reviews the data collected to date on alcohol drinking behavior and other alcohol‐related behaviors in sP and sNP rats. The behavioral profile of sP rats is also compared with that of other lines of selectively bred alcohol‐preferring rats and the heterogeneity resulting from this comparison is discussed in terms of different animal models for the different forms of alcoholism.
Repeated administrations of lithium salts (Li2CO3 or LiCl, 60 and 85 mg/kg, respectively, twice a day for five days) to rats increased brain 5-hydroxyindoleacetic acid (5-HIAA) by about 80% and brain serotonin by 15 to 20%. The changes were not due to an inhibition of 5-HIAA transport from brain, but to an increase in the rate of synthesis of brain serotonin. Rate of serotonin synthesis was measured by multiplying the rate constant of 5-HIAA decline, after inhibition of monoamine oxidase, by the steady-state level of 5-HIAA. The calculation indicated that lithium increased the synthesis rate of brain serotonin by about 80%. Moreover, chronic treatment with lithium salts also increased the levels of brain tryptophan by about 70%, suggesting that this could be the mechanism by which lithium stimulates serotonin synthesis.
