Low dose apomorphine induces context-specific sensitization of hypolocomotion without conditioning: support for a new state dependent retrieval hypothesis of drug conditioning and sensitization.

High doses of apomorphine induce sensitization to locomotor stimulant effects whereas low doses induce locomotor inhibition. We examined whether repeated low dose apomorphine induced sensitization and conditioning to the locomotor inhibitory effect. Three doses of the D1/D2 agonist, apomorphine, were used in a Pavlovian conditioning protocol: 0.05 mg/kg (autoreceptor level), 0.5 and 2.0 mg/kg (post-synaptic level). Rats received 5 daily apomorphine treatments paired or unpaired to an open-field environment (conditioning phase) followed by a saline test (conditioning test) and an apomorphine challenge test (sensitization test). Locomotion was measured for 30 min. During the acquisition phase, the 0.05 mg/kg paired treatment decreased locomotion while the high dose paired treatments increased locomotion. The 0.05 mg/kg paired treatment did not induce conditioning but induced inhibitory locomotor sensitization. The post-synaptic paired treatments produced conditioned and sensitized locomotor stimulation. For the low dose results, we propose an expanded contextual stimulus, which includes interoceptive drug cues. In the sensitization test, the same interoceptive drug cues and test environment cues are present as those during acquisition. In the conditioning test, normative dopaminergic activity is present which generates internal cues that may or may not generalize to the drug-induced cues and, permit or prevent retrieval of conditioning.