Invited Symposium: What Can Genetic Models Tell Us About Attention-Deficit Hyperactivity Disorder (ADHD)?
The behavioural disturbances of Attention-Deficit Hyperactivity Disorder (ADHD) have been attributed to dysfunction of the mesolimbic dopaminergic (DA) projection from the ventral tegmental area of the midbrain. DA released from terminals in the nucleus accumbens (interface between limbic and motor areas of the brain) draws attention to unexpected, pleasurable events and provides the motivational drive for reward-related behaviour. An in-vitro superfusion technique was used to show that depolarization(25 mM K+)-induced release of DA from nucleus accumbens slices of spontaneously hypertensive rats (SHR, animal model for ADHD) was significantly lower than that of Wistar-Kyoto controls (WKY). Evidence also suggested that DA autoreceptor efficacy was increased at low endogenous agonist concentrations. D2-receptor blockade by the antagonist, sulpiride, caused a significantly greater increase in the electrically stimulated release of DA from nucleus accumbens slices of SHR compared to WKY. This suggested that presynaptic regulation of DA release had been altered in SHR to cause down-regulation of the DA system. This could have occurred at an early stage of development in an attempt to compensate for abnormally high DA concentrations. The reduction in DA transmission could have left the adult SHR with impaired DA reward/reinforcement mechanisms, resulting in the behavioural disturbances characteristic of ADHD.
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|Russell, VA; (1998). The Nucleus Accumbens Motor-Limbic Interface of the Spontaneously Hypertensive Rat (SHR) as Studied In-Vitro by the Superfusion Slice Technique. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/sadile/russell0341/index.html|
|© 1998 Author(s) Hold Copyright|