Effects of TRH and an analog, DN-1417 on the activities of single neurons in the nucleus accumbens, cerebral cortex and caudate-putamen of rats.

The actions of TRH and its analog, y butyrolactone y -carbonyl histidyl prolinamide citrate (DN-1417) on the unit activities of the cerebral cortex, caudate -putamen and nucleus accumbens were examined using a microelec trophoretic technique in anesthetized rats. Over 80% of the neurons examined in the nucleus accumbens responded to TRH and DN -1417. The effects were mainly inhibitory, but excitatory effects (12-17%) were also detected. In the cerebral cortex and caudate -putamen, only one-third of the neurons were depressed by TRH and DN-1417. DN-1417 exerted an effect similar to TRH on almost all neurons. Dopamine affected almost all neurons. Its main effect was inhibition, but excitation was also observed in some neurons of the nucleus accumbens. Methamphetamine mimicked dopamine in the three regions. However, it was observed that TRH and DN-1417 mimicked dopamine only in the nucleus accumbens neurons. Furthermore, both the inhibitory and excitatory actions of TRH, DN -1417 or dopamine were attenuated by the dopamine receptor antagonist, haloperidol, which was administered systemically. These results suggest that : (1) TRH and DN -1417 have similar actions on the neurons; (2) TRH and DN-1417 act more selectively than dopamine and methamphetamine on the nucleus accumbens neurons, and they may act indirectly on dopaminergic neurons of the nucleus accumbens through an action on presynaptic sites; (3) Endogenous TRH may play a physiological role as a neuromodulator of dopaminergic transmission in the nucleus accumbens.