Classical conditioning of morphine hyperthermia was examined using an explicit conditioned stimulus (CS) paired with intravenous (IV) morphine administration. Rats were implanted with a jugular vein cannula and a biotelemetry device for monitoring body temperature. The animals were housed 24 h/day in the chambers in which all testing occurred. The CS was a 15-min light/noise stimulus. The unconditioned stimulus (US) was an infusion of morphine (5 mg/kg). Rats were assigned to either the Paired group, which received morphine with the CS, or the Unpaired group, which received explicitly unpaired presentations of the CS and US. The CS-morphine pairings resulted in development of a conditioned hyperthermic response in the Paired group evoked by the CS in the absence of morphine. The development of morphine hyperthermia was more rapid in the Paired group in the presence of the CS than in its absence in the same group and more rapid in the Paired group than in the Unpaired group during the CS. These results clearly show that learning affects the response to morphine administered repeatedly. In contrast to previous studies, conditioned hyperthermia was elicited within 15 min by a discrete CS in a situation where the response was not confounded by handling or the stress of injection.
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