Effects of morphine and naloxone on thresholds of ventral tegmental electrical self-stimulation

Summary The involvement of opioid systems in self-stimulation reward was investigated by studying the effects of the opioid antagonist naloxone (10 mg/kg s.c.) and graded doses of morphine (0.3–5.0 mg/kg s.c.) on intracranial electrical self-stimulation (ICSS) in rats with electrodes in the ventral tegmental area. Lever pressing for ICSS was analyzed using three different procedures: (1) determination of response rate i.e. the number of responses to high and threshold currents, (2) measuring threshold current when response rate was kept low and relatively constant, (3) determination of behavioural threshold using a two-lever procedure in which a response on one lever resulted in a reset of the decreasing current to a high current contingent on a response to the other lever. It was found that low doses of morphine increased the response rate of ICSS behaviour and decreased the threshold whereas the higher doses decreased the response rate but also decreased the threshold current when measured with a rate insensitive procedure. Naloxone raised the threshold for ICSS and caused a corresponding decrease of response rate.In a second series of experiments in which the behaviour of rats which had been tested in one procedure was analysed using one of the other methods, it was observed that naloxone caused smaller changes, while the effects of morphine were at least comparable to those observed in the first series of experiments.The present data suggest that response rate insensitive procedures to analyse ICSS should be preferred to response rate sensitive ones, especially when the interaction of depressant drugs such as morphine with reward mechanisms is investigated. It is concluded that opioid systems are involved in ICSS elicited by electrical stimulation in the ventral tegmental area, and that the synergistic action of electrical stimulation and the pharmacological activation of ICSS reward circuits due to morphine may be related to the addictive properties of this drug.