The nucleus accumbens motor-limbic interface of the spontaneously hypertensive rat as studied in vitro by the superfusion slice technique.
The behavioral 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, behaviorally significant events and provides the motivational drive for reward-related behavior. 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 behavioral disturbances characteristic of ADHD.
Russell
V A
VA
Department of Physiology, University of Cape Town, Medical School, South Africa. russell@physio.uct.ac.za
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D066298:In Vitro Techniques; D008032:Limbic System / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR
D004298:Dopamine