The effects of different 4-aminopyridine and morphine combinations on the intensity of morphine abstinence

Abstract

The glutamatergic system is deeply involved in the development of opiate dependence and in the manifestation of opiate abstinence syndrome. In this study the effect of the increase in the endogenous glutamate (GLU) release due to 4-aminopyridine (4-AP), a potassium channel blocker, during the development of morphine (M) physical dependence and during the naloxone (NL)-precipitated abstinence syndrome was investigated. For the development of physical dependence M was intraperitoneally (i.p.) injected for 9 days 105 min following i.p. saline administration to a group of rats. In the first 3 days the dose of M was 10 mg kg(-1). In the second 3 days the initial dose was doubled (20 mg kg(-1)) and in the last 3 days the dose of M was raised to 40 mg kg(-1). On day 10, the rats were divided into three groups at random and these three groups were i.p. given saline 105 min before 80 mg kg(-1) M, 2 mg kg(-1) 4-AP 105 min after 80 mg kg(-1) M, and 80 mg kg(-1) M 105 min before 2 mg kg(-1) 4-AP, respectively.