Modification of the drug-taking behavior in rats by interference in the metabolism of 5-hydroxytryptamine and catecholamines

Abstract

Forty naive female rats had the choice between drinking either tap water or 0.3 mg/ml levorphanol in saccharose solution. Nine animals preferred the levorphanol/saccharose solution which, on average, comprised 83% of their total fluid intake, and became physically dependent. In order to assess the influence of the sweet taste on the drug-taking behavior of these rats, the saccharose concentration of the levorphanol solution was subsequently lowered in three steps from 17% to 0%. Down to 5% saccharose no significant difference in the daily levorphanol intake could be observed. On average 77% of the total fluid intake (~53.0 mg/kg) was due to the levor-phanol solution. Without saccharose the levorphanol consumption diminished to 10% (~3.9 mg/kg), i.e., the aversion to the bitter taste of the opioid obviously counteracted the possibly positive reinforcement effect of the drug. After subtotal destruction of noradrenaline and dopamine neurons by intraventricular injection of 6-hydroxydopamine the levorphanol consumption (8% saccharose) was reduced to 53% of the total fluid intake (~24.8 mg/ kg). The same effect occurred after interference with the 5-hydroxytryptamine metabolism by 320 mg/kg p-chlorophenylalanine (~25.8 mg/kg) indicating that voluntary drinking of levorphanol/saccharose solution in levorphanol-dependent rats is not only due to a preference for saccharose.