Project: Research project

Project Details


The consequences of drug abuse range from disruptive to devastating,
affecting the health and ell-being of individuals, families, communities
and nation. Intervention at athe individual level, with better methods of
prevention and treatment, offers what may be the best hope for
amelioration. But effective treatments require a better understanding of
the mechanisms underlying the reinforcing power of drugs. Recent years
have seen substantial gains in understanding the molecular mechanisms
through which abused drugs influence the CNS. A number of specific brain
structures have been implicated. In particular, the dopaminergic neurons
of the ventral tegmental area (VTA) and their projection regions, including
the nucleus accumbens (NAc) have been strongly implicated in the
reinforcing effects of cocaine, as well as opiates, benzodiazepines,
barbiturates and ethanol. But relatively little is known about the
function of the VTA in awake, behaving animals. In particular, few
experiments have examined the activity of VTA neurons during motivated
behavior, and to our knowledge, none have extended these observations to
the influence of cocaine or other abused drugs. In preliminary
experiments, we found that VTA neurons showed systematic variations in
firing rate associated with ongoing reward-seeking and consumption. For
some neurons, cocaine enhanced both the excitatory and inhibitory phases of
behaviorally correlated activity in the VTA. It is possible that this
enhancement reflects an increased sensitivity to rewarding in general in
the presence of cocaine. However, not all neurons responded to cocaine in
this fashion: indeed, a considerable variation in response was observed.
The VTA is known to include several distinct neural subtypes, and it is
possible that this variability reflect recordings from these different
neurons. Alternatively, the observed variability could accurately reflect
normal information processing in the VTA. In the proposed studies, the
activity of multiple single neurons will be simultaneously recorded from
chronically implanted microwire electrodes in the ventral tegmental area
(VTA). Basic electrophysiological characteristics will be determined for
neurons recorded in rats under anesthetic and awake, and given drugs whose
actions on VTA have been well characterized, and which are known to
differentiate subtypes of TA neurons. These will allow direct comparison
of results using the current method to previous studies, and direct
comparison of responses in the anesthetized and awake rat. In addition, a
better estimate of the number and nature of VTA neuronal subtypes can be
derived, as well as strategies for the identification of these neurons that
can be used in future experiments utilizing chronically implanted microwire
electrodes. In further experiments, selected rats will be successively
tested in three behavioral paradigms; 1) Signalled non-contingent
presentation of sucrose solution, 2) pressing a lever for access to sucrose
solution, and 3) extinction of lever pressing. These experiments will
allow assessment of the behavioral associations of neural firing rates, and
provide insight to the functional significance of VTA neuronal subtypes.
Effective start/end date5/1/944/30/97


  • National Institutes of Health
  • National Institutes of Health: $75,000.00
  • National Institutes of Health


  • Medicine(all)

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