INHIBITION OF TAIL-FLICK AND SHAKING RESPONSES BY INTRATHECAL AND INTRAVENTRICULAR D-ALA2-D-LEU5-ENKEPHALIN AND BETA-ENDORPHIN IN ANESTHETIZED RATS

Publisher Website
Google Scholar
Abstract
The potencies of D-Ala2-D-Leu5-enkephalin (DADL) and .beta.-endorphin (.beta.-EP) injected intrathecally and i.c.v. [intracerebroventricularly] on the inhibition of tail-flick and ice water-induced shaking responses in pentobarbital-anesthetized rats were studied. Peptides were injected stereotaxically into the 3rd ventricle or into the spinal subarachnoid space. The tail-flick response was measured 10 or 20 min after the injection of DADL or .beta.-EP, respectively, after which the rats were immersed for 5 min in ice water and the number of shakes was counted. Intrathecal DADL and .beta.-EP were equipotent in inhibiting both the tail-flick and shaking responses. Treatment with naloxone (2 mg/kg i.p.) shifted the dose-response curve for both responses to the right more for the .beta.-EP than for DADL. Unlike the equipotency intrathecally, DADL i.c.v. was less potent than .beta.-EP in inhibiting both the tail-flick and shaking responses. Previous results in the unanesthetized rat had also shown that i.c.v. DADL was less potent than .beta.-EP in inhibiting the tail-flick responses. The spinal cord is sensitive to both DADL and .beta.-EP, whereas the supraspinal area is more sensitive to .beta.-EP. Because the potency of i.c.v. .beta.-EP for inhibiting tail-flick but not shaking was substantially reduced in anesthetized compared to unanesthetized rats, the neuronal substrates involved in inhibition of shaking are different from those of inhibition of the tail-flick. The different sensitivities to i.c.v. vs. intrathecal administration and the unequal response to the antagonistic action of naloxone indicate that DADL and .beta.-EP produce their action through different opioid receptors.