The effect of long-term oral combination of methylphenidate and reserpine on the autonomic phenomena at rest and on inborn and acquired reflexes of dogs

Summary

The influence of long-term oral medication of 0.02 mg/kg reserpine daily in combination with 0.2, 0.5 and 1.0 mg/kg of methylphenidate on autonomic phenomena at rest, on the unconditioned and conditioned alimentary reflex and its differentiation were investigated in 4 dogs in 228 experiments.

Intoxication symptoms appeared in the third week of daily administering 0.02 mg of reserpine. Combination with methylphenidate did not prevent or remove intoxication. After a month of reserpination one dog died.

Long-term combination of oral medication changes the autonomic phenomena at rest and during the reflexes in the same way as medication with reserpine alone. Methylphenidate merely balances the effect of reserpine on the conditioned salivation and this only in the first period of combined medication. After combined medication has ended, the influence of the reserpine does not last, as it does after medication with reserpine alone, but the autonomic phenomena at rest, during acquired reactions and their differentiations return to normal and sometimes even overshoot. The characteristic effect of medication of methylphenidate alone — improved differentiation with simultaneous increase of conditioned reflexes — does not occur either during combined medication nor after its termination.

The results of our investigations indicate that:

• 1. Long-term administration of reserpine decreases the adaptibility of the organism to its surroundings, apparently because the adrenergic mechanism of the mesodiencephalic part of the reticular formation, which plays an important role in the electrophysiological mechanism of arousal, also participates substantially in the acquired reflexes and their differentiations.

• 2. Methylphenidate on its own causes better adaptation of the organism to its surroundings apparently by acting through the catecholamines on the adrenergic mechanism of the mesodiencephalic region. In the case of long-term combination with reserpine methylphenidate cannot be effective because the content of catecholamines of the tissue of the reticular formation is substantially diminished.

• 3. The slowly increasing concentration of catecholamines after simultaneous ending the medication of both substances apparently enables the remnants of methylphenidate to have a sympathomimetic effect.