The effects of dopaminergic agonists and antagonists on the frequency-response function for hypothalamic self-stimulation in the rat.

The function of dopaminergic synapses in generating the reinforcing effect of brain stimulation was examined in 8 rats. The animals were implanted with bipolar electrodes and trained to press a bar for lateral hypothalamic stimulation. The frequency of stimulation pulses was systematically changed, and a frequency-response curve was plotted for each rat after intraperitoneal injection of a test agent. Dopamine agonists and antagonists selective to either D1 or D2 subtypes of receptors were used. The curve was shifted to a high-frequency range by either SCH 23390 (D1 antagonist) or raclopride (D2 antagonist). SKF 38393 (D1 agonist) failed to shift the curve, and quinpirole and CV 205-502 (D2 agonists) shifted the lower part of the curve to a low-frequency range. The results suggest that an activation of D2 receptors generates a reinforcing effect, and that the effect is expressed only if D1 receptors are activated to an optimal level.