While it is well known that rats can discriminate a peripheral injection of morphine from a saline injection, to our knowledge no one has trained rats to discriminate a direct brain-site injection of morphine from saline. In the present series of studies, one group of rats was trained to discriminate morphine (0.3 μg) from saline injected into the perifornical area of the hypothalamus (PFA), a process that took rats about 37 sessions to learn. A dose response generalization curve for PFA-injected morphine (0.01, 0.03, 0.1, and 0.17 μg) was generated in which the two highest doses of morphine generalized to the morphine-appropriate training stimulus. Intraperitoneal (i.p.) injection of 3 mg/kg, but not 1 mg/kg morphine, resulted in morphine-appropriate responding in the PFA morphine-trained rats. A second group of rats was trained to discriminate i.p. injections of 3 mg/kg morphine from injections of saline. A dose-response generalization test for i.p.-injected morphine (0.3, 0.56, 1.0, and 1.7 mg/kg) was conducted in which the 0.17 mg/kg dose of morphine generalized to the morphine-appropriate training stimulus. Generalization tests using PFA-injected morphine doses (0.17, 0.56, 1.0, and 3.0 μg) failed to result in morphine-appropriate responding in the i.p. morphine-trained rats. Naloxone administered into the PFA (50 μg) or the periphery (3 mg/kg, i.p.) blocked morphine discrimination in the PFA-trained rats. However, when naloxone was injected into the PFA (50 μg) together with i.p. morphine (3 mg/kg) in animals trained using i.p. injections, the antagonist failed to block morphine-appropriate responding. Thus, while peripheral injection of morphine generalized to the discriminative stimulus effects of morphine produced under PFA-injection training, the opposite effects were not noted. Copyright (C) 1999 Elsevier Science B.V.
Bibliographical noteFunding Information:
This work was supported by a Department of Veterans Affairs Merit Award (JPC and ASL). P. Dittel was supported by a Research Experience for Undergraduate Grant (NSF SBR-96-00021) and E. O'Hare was supported under DA-07097. Additional support was provided by DA-03999 (ASL). We thank Dr. David Jewett for his assistance in the preparation of this manuscript.
- Paraventricular nucleus
- Perifornical area