The abuse of opiate drugs by humans represents a serious social and economic problem. It is clear that the abuse of such drugs is related to their ability to produce """"""""reward"""""""", and there is ample evidence to suggest that the CNS region of the nucleus accumbens septi (NAS) is critical in this regard. Yet, other evidence suggests that opiates may produce """"""""reward"""""""" either directly within the NAS or indirectly by NAS effects on NAS afferent nuclei. The hypothesis of this research proposal is that the neuropharmacological actions of opiates on NAS neurons are the basis of opioid reward. Since previous electrophysiological evidence shows that systemic opiate effects may involve only a subset of NAS neurons, I will identify, by electrophysiological criteria, those neuronal subpopulations affected by systemically administered opiates, and determine whether such effects are direct or indirect. Single neurons in the NAS of anesthetized rats will be identified by their specific patterns of response to amygdala, ventral pallidal and midline thalamic nuclei stimulation. These NAS afferent nuclei are targeted because they are known opioid links to the NAS. The effects of systemically administered on the firing rate and response patterns of these NAS-evoked cellular responses will then be examined. The direct vs. indirect actions of these systemic drug effects will then be assessed by examining 1) the direct effects of iontophoretically applied opiates on these NAS-evoked responses, and 2) the indirect effects of locally micro-infused morphine into the VTA on these NAS neurons. The VTA is an NAS afferent nucleus known to be opiate sensitive and to exert modulatory influences on NAS activity. 3) The potential interaction between evoked responses produced by stimulation of these NAS afferents and the application of opiates by any of the above routes will also be examined. Information gained from these studies will bear directly on the role of the NAS in opioid drug reward.
| Hakan, R L; Eyl, C; Henriksen, S J (1994) Neuropharmacology of the nucleus accumbens: systemic morphine effects on single-unit responses evoked by ventral pallidum stimulation. Neuroscience 63:85-93 |
| Hakan, R L; Hart, C; Eyl, C (1993) Specific neurophysiological effects of systemic nicotine on neurons in the nucleus accumbens. Synapse 15:191-7 |
| Hakan, R L; Berg, G I; Henriksen, S J (1992) Electrophysiological evidence for reciprocal connectivity between the nucleus accumbens septi and ventral pallidal region. Brain Res 581:344-50 |
