Responding for rewarding brain stimulation: cocaine and isradipine plus naltrexone.

Rats, fixed with chronically indwelling electrodes for electrical intracranial stimulation (ICS) of the lateral hypothalamus, were taught to press a bar for ICS. Once pressing rates became stable, during daily 20-min sessions, rats were given cocaine (5 or 20 mg/kg) before the sessions. When given daily, cocaine consistently enhanced rates of pressing. When a combination of small doses of isradipine (e.g., 1 mg/kg) and naltrexone (3 mg/kg) were given before cocaine administration. the combination blocked cocaine's enhancement of pressing for ICS. The combination, however, neither reduced rates of pressing below those observed under placebos (i.e., baseline conditions) nor reduced rates when no cocaine was given. Naltrexone and isradipine (in the dose used in the combination) by themselves did not block cocaine's effects. This profile of effects indicates that a combination of isradipine and naltrexone is apt to be useful in treating cocaine use disorders.

Combination of naltrexone and fluoxetine on rats' propensity to take alcoholic beverage.

Naltrexone (NTX) and fluoxetine (FLU) are useful for treating alcoholism and depression, respectively. Furthermore, these afflictions covary. Given the possibility that people might be prescribed NTX and FLU concurrently, we assessed the effects of these two agents on rats' propensity to drink an alcoholic beverage. Rats were given 65 days of access to a sweetened alcoholic beverage and water for 2 hr daily. At first, they took little ethanol, but after 20 days, they took on average 2.0 to 2.5 g/kg of ethanol, daily during the 2-hr session. They also took sufficient water to maintain their health. After 30 days, they were divided into four groups to receive, 30 min before the drinking session, 1 of 4 different kinds of injections. For the next 20 days, one group received placebo daily. Another group received 5 mg/kg of NTX daily and another 5 mg/kg of FLU daily. The fourth group received both 5 mg/kg of NTX and 5 mg/kg of FLU daily. After 20 days, the doses of NTX and FLU were doubled across an additional 10 days. Both NTX and FLU reduced rats' intake of alcoholic beverage. The combinations of NTX and FLU, however, were no more effective in reducing rats' intake of alcoholic beverage than either alone. Also, the small dose of NTX seemed to lose its effectiveness with repeated administrations. A second experiment confirmed the conclusion that small doses of NTX lose their effectiveness in suppressing intake of alcoholic beverage across repeated administrations. In summary, data provide no support for the idea that FLU and NTX would act synergistically to reduce propensity to take alcoholic beverages.