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Two models may outline glutamate-dopamine interactions between the BLA and NAS. We investigated, via D1-D2 agonist cocktail injections, whether dopamine acts as a modulator or mediator in these interactions. Electrical intracranial self-stimulation (ICSS) of the amygdala was used. The rats usd as test subjects had an electrode implanted in their left basolateral amygdala and a pair of cannulae bilaterally placed in the nucleus accumbens. The drugs administered in the D1-D2 cocktail were SKF38393 (D1) and quinporole (D2). One and 3 microgram doses (1 microliter in volume) of the cocktail were made into the accumbens ipsilaterally and contralaterally to the electrode in rats previously trained to self-stimulate. If the cocktail enhanced stimulation reward via modulation, there would be an increase in responding only after the ipsilateral injection. If dopamine was the "reward transmitter," a decrease in responding was expected. The result, over the two doses tested, was that there was no significant change in responding. This implies that dopamine neither modulates nor mediates the reward of basolateral amygdala stimulation.
The amygdala plays an important part in functions that correspond with reward in the brain. Its interaction with the nucleus accumbens, a structure previously shown to be very involved in brain reward, may be important. It is known that the axonal projection from the basolateral amygdala to the nucleus accumbens uses glutamate as the transmitter. In addition, dopamine in the nucleus accumbens has been heavily implicated in brain reward. There are two possible models that outline the interactions between dopamine and glutamate in the nucleus accumbens. One model describes dopamine as a modulator of the glutamate, which is carrying the "reward signal." Another model describes the dopamine as the carrier of the reward signal. If dopamine carries the reward signal for amygdala stimulation, injection of agents that directly excite dopamine receptors in the accumbens should interfere with normal transmission and decrease responding for that stimulation. If dopamine is modulating a glutaminergic reward signal, injection of these agents should increase responding. In this experiment, an attempt was made to stimulate all subtypes of dopamine receptors by inkecting drugs which selectively stimulate both the D1 family (D1, D5) and the D2 family (D2, D3, D4) in a cocktail.
Animals Eight adult male Sprague-Dawley rats were selected for the experiment. They weighed approx. 350g at surgery. In the surgical procedure, eacxh had a bipolar stainless steel electrode implanted into their left basolateral amygdala (BLA), as well as a pair of guide tubes implanted bilaterally into the medial core of the nucleus accumbens (NAS). Procedure After a week-long recovery period, an ICSS training period occured in whch the rats acquired operant conditioning. The ICSS testing utilized a nose poke apparatus in which the rats put their noses into a hole that detects the insertion, delivering a 150 msec burst of 0.5 msec biphasic square waves, at 100 pps, to the electrode. After the rats' numver of responses stabilized, sham and saline injections into the NAS were made. Ipsilateral and contralateral SKF38393-quinporole (D1 and D2 agonists, respectively) cocktail injections were then performed on four of the rats in 1 and 3 microgram (1 microliter in vol.) doses. These injections were made by lowering a 30 gauge stainless steel tubing into the accumbens and infusing the drug solution. The rats were then observed for their rate of ICSS. Testing was conductedin 20 min. sessions, once daily.
The drug effect on ICSS was determined by the change in responding compared to the immediately preceding control session. This was done for the saline vehicle, 1 microgram, and 3 microgram doses. The injections did not produce a chnga significantly different from the saline vehicle. Furthermore, there was not a reliable difference between ipsilateral and contralateral injections.
- Injections of a D1-D2 agonist cocktail into the nucleus accumbens did not reliably change self-stimulation of the basolateral amygdala.
- The responding did not change in a direction consistent with either a modulatory or mediatory role of dopamine transmission.
- It would appear that the reward of electrical stimulation of the basolateral amygdala is not based on dopaminergic transmission in the nucleus accumbens.
I would like to thank Dr. Neill, Donn Simmons, and the department of Psychology at Emory University. This material is based upon work supported by the Howard Hughes Medical Institute under Grant No. 52003071 and by the National Science Foundation under STC Grant No. #IBN-9876754.
Johnson used electrical self stimulation to the amygdala region of the brain in rats to observe changes in the animal's level of response. Two principle neurotransmitters, dopamine and glutamate, are important in the brain functions responsible for reward; the purpose of the experiment was to determine the role of each, particularly dopamine, in the brain's reward circutry. If the responses were to increase, dopamine would be confirmed as a modulator; the opposite would confirm it as a carrier of the rewaed signal. Experimentation revealed no significant change in responding, therefore not validating any of the models.
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