Conditioned Diminution of the Unconditioned Response in Rabbit Eyeblink Conditioning: Identifying Neural Substrates in the Cerebellum and Brainstem

Several models of Pavlovian conditioning assume that processing of an unconditioned stimulus (US) is diminished by a conditioned stimulus (CS) with which it had been paired. Two experiments evaluated the hypothesis that US processing may be diminished by CS-dependent activation of the cerebellum. Experiment 1 showed that electrical brain stimulation (EBS) of the cerebellar interpositus nucleus diminished the peak amplitude of the rabbit's unconditioned eyeblink response. This effect was bilateral, was systematically related to the intensity of EBS, maximal 50 ms after the offset of EBS, and substantially reversed by naloxone. Experiment 2 showed that inactivating the contralateral red nucleus with γ-d-glutamylglycine blocked the decremental effect of interpositus stimulation. Implications for neural systems mediating the inhibitory effects of cerebellar activation and the antinociceptive role of noradrenergic and opioid systems in Pavlovian conditioning phenomena are discussed.