alpha(2)-Adrenoceptor antagonists and propensity to take alcoholic beverages.

Rats were maintained on a daily regimen involving a 2h opportunity to take both water and a sweetened alcoholic beverage (12% ethanol, 0.25% saccharin). After 3 weeks on this regimen, rats regularly take substantial amounts of alcohol. After stabilization, injections of alpha(2)-adrenergic antagonists were administered, 15min before the opportunity to drink. Yohimbine and methoxyidazoxan dose relatedly decreased intake of alcoholic beverage and increased intake of water. In Experiment 2, a number of rats were taken off the daily regimen for 9 days, then returned to it. Across the first 12 days of the reinstated daily regimen, half the rats received placebo and half methoxyidazoxan. The group receiving placebo rapidly returned to taking large amounts of alcoholic beverage while the group receiving methoxyidazoxan did not. In Experiment 3, it was shown that a dose of methoxyidazoxan that decreased intakes of alcoholic beverage did not decrease intakes of other palatable beverages. In Experiment 4, it was shown that yohimbine persistently reduced intakes of alcoholic beverage with daily administration. These results indicate that alpha(2)-antagonists might be effective pharmaceutical adjuncts to other treatments for alcohol abuse and alcoholism.

Speed and consistency of human decisions to swallow or spit sweet and sour solutions.

Measurements of the frequency and speed of spitting or swallowing citric acid, sodium saccharin, or mixture solutions, using the taste of one of them as the definition of what was to be spit, revealed that 'correct' spits occurred on > or = 70% of trials with equal reliability and latency among the liquids, indicating that recognition-based rejection decisions in adult humans are as rapid and consistent for an arbitrary sweet taste as for a sour or mixed taste.

MDMA produces a conditioned place preference and elicits ejaculation in male rats: a modulatory role for the endogenous opioids.

Methylenedioxymethamphetamine (MDMA) can produce a conditioned place preference (CPP) among rats. The ability of MDMA to produce a CPP was assessed while some rats were under the influence of naltrexone, 56 mg/kg, given 4 h before conditioning. Naltrexone attenuated MDMA's ability to produce a CPP without completely blocking MDMA's effects. Having noticed previously the production of seminal plugs by rats receiving MDMA, the presence of seminal plugs was recorded across the 8 days of conditioning. Roughly half of the rats receiving 6.3 mg/kg of MDMA left plugs during the conditioning period, while over two-thirds of those receiving a combination of MDMA and naltrexone left plugs. A second study, assessing further doses of MDMA, tabulated the drug's effects on the production of seminal plugs across 3 h. Besides eliciting ejaculation, MDMA also led to increased urination and defecation and a loss of body weight. These results support suggestions that the endogenous opioids modulate the reinforcing properties of stimulant drugs and affect male sexuality.

Tests of opioid deficiency hypotheses of alcoholism.

Eighty-three male rats were maintained on a daily regimen involving 22 h of deprivation of fluids followed by 2 h of access to water and a sweetened alcoholic beverage (12% ethanol, 5% sucrose). After about 3 weeks of such a regimen, rats eventually take considerable amounts of ethanol daily. In the present study, a series of injections of opioids was given subsequent to establishing stable daily intakes of ethanol. Specifically, before a day's opportunity to take fluids, some rats were given a small dose of morphine (2.0 mg/kg), while others were given a dose of naloxone (4.0 mg/kg). When morphine was given 0.5 h before the opportunity to drink, intake of ethanol was increased. However, when morphine was given 4.0 h before the opportunity, intake of ethanol was decreased. Nearly opposite effects were observed when naloxone was given. Other experiments tested the effects of giving morphine 4.0 h before the opportunity to drink plus the effects of a small dose of naloxone or plus the effects of a small dose of morphine. Morphine given 4.0 h before potentiated the effects of a small dose of naloxone and attenuated the effects of another dose of morphine. The effects of morphine were also shown to be similar among rats taking a solution of ethanol and water rather than a sweetened solution. These data provide support for the idea that surfeits, not deficits, in opioidergic activity increase propensity to take alcoholic beverages.