Asymmetrical effects of morphine and naloxone on reward mechanisms

Rats with bilaterally implanted lateral hypothalamic electrodes were tested daily for self-stimulation to each side of the brain, and rotation (circling behavior) was recorded concomitantly. All rats rotated in a preferred direction regardless of the side of the brain stimulated and all rats had asymmetries in self-stimulation sensitivity related to the direction of rotation. Morphine increased rotation and lowered self-stimulation thresholds at low doses (e.g., 2.5 mg/kg) and decreased rotation and raised self-stimulation thresholds at high doses (e.g., 20.0 mg/kg). The changes in self-stimulation thresholds preferentially occurred on opposite sides of the brain, i.e., the low-dose decrease in thresholds was greater in the normally less sensitive side of the brain whereas the high-dose increase in thresholds was greater in the normally more sensitive side of the brain. Naloxone produced no changes in rates of rotation but did elicit small changes in self-stimulation that varied with the side of the brain, i.e., dose-related decreases in thresholds occurred in the normally more sensitive side of the brain whereas dose-related increases in thresholds occurred in the normally less sensitive side of the brain. Subsequently rats were tested in a choice procedure providing concurrent access to rewarding stimulation of either side of the brain; currents were titrated such that, under baseline conditions, rats continually alternated between self-stimulating one side of the brain or the other. Morphine induced a preference for the less sensitive side of the brain that was comparable in magnitude at all doses and independent of its biphasic effects on rates of responding. Naloxone induced a dose-related preference for the more sensitive side of the brain while not altering rates of responding. Naloxone (1.0 mg/kg) also completely antagonized the effects of all doses of morphine. The results are discussed in terms of lateralized actions mediating the discriminable effects of reinforcing drugs.