Pavlovian Conditioning of Morphine Hyperthermia: Assessment of Interstimulus Interval and CS-US Overlap

The present study examined the effect of interstimulus interval on acquisition of conditioned thermal responses produced by trials in which a light/noise stimulus (CS) was repeatedly paired with infusion of morphine sulphate (US). Rats were implanted with a chronic intravenous catheter for drug delivery and a biotelemetry device for remote monitoring of core body temperature. In experiment 1, different groups received morphine either 0.5 (group P0.5) or 15 min (group P15) after onset of the 15-min CS. A third group was exposed to an identical number of CS and US presentations but in an explicitly unpaired manner (group UP). After repeated exposure to morphine, all groups showed a more rapid rise in body temperature in response to drug infusion. Test presentations of CS alone revealed conditioned hyperthermic responses to CS in groups P0.5 and P15. However, the response of the P15 group was smaller than that of the P0.5 group, suggesting weaker conditioning at the longer interstimulus interval. The contribution of CS-US overlap to the diminished associative strength observed in the P15 group was assessed in experiment 2. Groups P0.5/15 and P0.5/30 received infusions of morphine 0.5 min after onset of a 15- or 30-min CS, respectively. Group P15/30 received morphine 15 min after onset of a 30 min CS, whereas group UP/30 received explicitly unpaired presentations of the US and a 30-min CS. Enhancement of the hyperthermic effect of morphine was observed in all groups after ten conditioning trials. Test presentations of the CS without drug revealed that all paired groups had acquired conditioned hyperthermic responses. These results support the conclusion that drug-induced conditioning can occur at relatively long interstimulus intervals when there is sufficient temporal overlap between the CS and unconditioned response evoked by the drug US.