Antinociceptive responses after microinjection of morhpine or lanthanum in discrete rat brain sites

Stereotaxic microinjections of morphine (10.5-105 nmol) or lanthanum (0.337-2.25 μmol) were made into four subcortical sites of the rat brain and antinociceptive responses were assessed using the tail-flick and hot-plate methods. Unilateral application of 21 nmol of morphine into the periaqueductal gray (PAG) region produced a maximal antinociceptive response which was antagonized by s.c. naloxone administration. Similarly, PAG administration of La⁺⁺⁺ also inhibited tail-flick and hot-plate nociceptive responses. La⁺⁺⁺-induced analgesia was significantly antagonized by comicroinjections of Ca⁺⁺ into the PAG and was also antagonized to a lesser extent by s.c. administered naloxone. Additionally, the analgetic responses produced by 10 mg/kg s.c. of morphine were significantly diminished after bilateral injection of 11 nmol of naloxone into the PAG. Interestingly, systemically administered morphine analgesia was also antagonized by a microinjection of Ca⁺⁺ into the PAG. Antinociceptive responses were also elicited by morphine or La⁺⁺⁺ injected into the lateral ventricle, posterolateral ventricle or fourth ventricle, although the magnitude of analgesia produced after ventricular injection was not as great as that associated with the PAG. These findings indicate that the similarities between the antinociceptive actions of morphine and La⁺⁺⁺ extend to common neuroanatomical sites of action and strengthen the hypothesis that alterations in the binding or movement of Ca⁺⁺ in restricted brain areas may be closely associated with the analgesic actions of the narcotic drugs.