Functional Interaction between the Shell Sub-Region of the Nucleus Accumbens and the Ventral Tegmental Area in Response to Morphine: an Electrophysiological Study

Abstract

This study has examined the functional importance of nucleus accumbens (NAc)-ventral tegmental area (VTA) interactions. As it is known, this interaction is important in associative reward processes. Under urethane anesthesia, extracellular single unit recordings of the shell sub-region of the nucleus accumbens (NAcSh) neurons were employed to determine the functional contributions of the VTA to neuronal activity across NAcSh in rats. The baseline firing rate of NAcSh neurons varied between 0.42 and 11.44 spikes/sec and the average frequency of spontaneous activity over 45-minute period was 3.21±0.6 spikes/sec. The majority of NAcSh neurons responded excitatory in the first and second 15-min time blocks subsequent to the inactivation of VTA. In the next set of experiments, eight experimental rats received morphine (5 mg/kg; sc). Three patterns of neuronal activity were found. Among the recorded neurons only three had an increase followed by morphine administration. Whereas the other three neurons were attenuated following morphine administration; and there were no changes in the firing rates of the two neurons left. Finally, unilateral reversible inactivation of VTA attenuated the firing activity of the majority of ipsilateral NAcSh neuron in response to morphine, except for a single cell. These results suggest that transient inactivation of VTA reduces the ability of neurons in the NAcsh to respond to systemic morphine, and that NAcSh neuron activity depends on basal firing rate of VTA inputs.

Keywords: Morphine; Nucleus Accumbens; Rat; Reversible Inactivation; Single Unit Recording; Ventral Tegmental Area.

Figure 1

(A) An example of spontaneous activity of neuron (2.16 ± 0.27 spikes/sec) recorded from the NAcSh in urethaneanesthetized rat. (B) Average firing rate of the NAcSh neurons in control (open circles), anesthetized rats (n = 18 to 29 neurons at each time point) at 5-min set intervals for the 45-min recording time period. Dash line shows the mean baseline activity (3.21±0.6 spikes/sec) in the NAcSh.

Figure 2

A typical effect of administration of 2%lidocaine (0.5µl) alone into the VTA on spontaneous activity of neurons in the NAcSh followed by saline (1 ml/kg; sc) injection. The firing rate of neuron continually recorded 90 min following injection of lidocaine at 45th-min of recording period.

Figure 3

Examples of the effect produced by morphine on NAc neurons recorded from anesthetized rats. The panel depicts the (A) decreasing firing rate and (B) increasing after morphine administration. In the bottom graph (c) neural firing rate didn't have any alteration.

Figure 4

Typical effects of intra-VTA administration of lidocaine followed by systemic injection of morphine. The upper figure (A) depicts neither lidocaine nor morphine didn't changed neural firing rate in NAsch. In the lower figure (B), lidocaine increased the NAcSh neural activity and firing rate decreased after morphine administration.

Figure 5

The histogram presents the average changes in percentage of firing rate of neurons in baseline recording and after intra-VTA injection of 2%lidocaine and lidocaine + morphine. Values expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 compared to saline respective group.