A small dose of morphine increases intake of and preference for isotonic saline among rats.

Water-deprived rats were given hourly opportunities to ingest physiological saline and water for a number of days until they were taking substantial amounts of both solutions. Prior to some opportunities to ingest, they were injected with either morphine (2.0 mg/kg) or a placebo. Across a variety of procedures, morphine increased intake of and, in 1-hr tests, increased preference for 0.9% NaCl. Intake of 1.5% NaCl also increased after administration of morphine. These data suggest that endogenous opioids are involved in sodium intake. These data also provide further support for the idea that one or more of the endogenous opioid systems are involved in the regulation of ingestion.

Further studies of opioids and intake of sweetened alcoholic beverage.

Rats were placed on a daily regimen of water deprivation followed by a limited opportunity to take either water or a sweetened alcoholic beverage. Across days of opportunity, they took less water and more alcohol until they were taking considerable amounts of alcohol. Naloxone, the classic antagonist at opioid receptors, was given prior to opportunity to drink and it reduced intakes of alcoholic beverage. Small doses of morphine, the classic agonist, increased intakes of alcoholic beverage at doses as low as 0.41 mg/kg. The effects of two other antagonists at opioid receptors (LY117413 and MR2266) were also tested. Both reduced intakes of alcohol. The data showing that more than one or two opioid antagonists reduce intakes of alcoholic beverages, even palatable beverages usually taken in large amounts, and that morphine increases intakes at very low doses, strengthen the idea that endogenous opioid systems are involved in modulating intake of alcohol.

Constant infusions of morphine and intakes of sweetened ethanol solution among rats.

Previous studies have indicated that injections of small doses of morphine increase rats' intake of solutions containing ethanol when rats have a choice of either water or a solution containing ethanol. In this experiment, rats which were implanted with osmotic pumps that delivered constant infusions of morphine (0.6 mg/kg/hr across 24 days) had elevated daily intakes of ethanol, as compared to controls, from the second day of opportunity to take the alcoholic beverage until the pumps were removed. In addition, half of the rats with pumps infusing morphine also received injections of morphine (1.0 mg/kg) just before the 1.5-hr opportunity to take alcoholic beverage or water every day for 8 days. Across this 8-day period, these rats took a mean of 5.18 g of pure ethanol/kg of body weight (g/kg) during the 1.5-hr opportunity to take the alcoholic beverage. This was reliably more than the mean of 4.02 g/kg that their counterparts (having morphine pumps and receiving injections of saline) took across the same period. These data support the hypothesis that a surfeit of opioidergic ligand may potentiate drinking of alcoholic beverages.

Opioidergic, serotonergic, and dopaminergic manipulations and rats' intake of a sweetened alcoholic beverage.

Groups of rats were maintained on a daily regimen of 22 h of water deprivation followed by a 2-h opportunity to take either water or a sweetened ethanol solution (ES). In one experiment, it was shown that previous morphine (M) dependence had no effect on initial daily intakes of fluids. After stable ES intakes were achieved, a variety of pharmacological manipulations were assessed for their effects on intake of the ES. Nalmefene, an opioid antagonist, dose-relatedly decreased intakes of ES, and was effective across days of injections. Fluoxetine (FX), a serotonergic reuptake inhibitor, also reduced ES intakes dose relatedly, and across days of injections, but the reduction was not as great as that seen with opioid antagonists. A small dose of M increased ES intakes when given in combination with an ineffective dose of FX, just as it does by itself. However, M had no effect on ES intakes in combination with an effective dose of FX. Pimozide (PIM), a dopaminergic antagonist, dose-relatedly decreased intakes of ES and water, and responding for positively reinforcing intracranial stimulation (ICS). When given in combination, M blunted PIM's reduction of ES intake, but had no effect on PIM's ability to decrease either intake of water or responding for ICS. Amphetamine did not reliably affect rats' intakes of ES across a range of doses. The data, in addition to previous work, lead to the idea that endogenous opioid systems are more salient, with respect to intake of alcoholic beverages, than the other tested neurotransmitter systems. Furthermore, the collective data suggest that a long-lasting opioid antagonist may be an effective pharmacological adjunct to other treatments for alcohol abuse and alcoholism.