Opiate infusion into nucleus accumbens: contrasting effects on motor activity and responding for conditioned reward.
In the present experiments, we examined the roles of opiate receptor subtypes in the nucleus accumbens in spontaneous motor behavior and responding for conditioned reward. Locomotor activity was measured using photocell cages and reward-related responding was determined in the conditioned reinforcement (CR) paradigm. In the CR paradigm, food-deprived rats were trained to associate a compound stimulus with food reward, and were subsequently tested for responding on a lever that resulted in presentation of the compound stimulus alone. In all experiments, various opiate agonists were microinjected into the nucleus accumbens. In the activity studies, morphine sulfate (mixed mu and delta agonist; 0.025, 0.25 and 2.5 micrograms/0.5 microliter) caused an initial inhibition followed by a disinhibition of activity while [D-Ala2-Met5]-enkephalin (DALA) (mixed mu and delta agonist; 0.25, 2.5 and 5.0 micrograms/0.5 microliter) elicited an immediate potentiation of locomotor activity. The behavioral profile following [D-Ala2-N-Me-Phe4-Gly-ol5]-enkephalin (DAMGO; mu agonist; 0.01, 0.1 and 1.0 micrograms/0.5 microliter) was similar to morphine. In contrast, [D-Pen2,5]-enkephalin (DPEN; delta agonist; 0.02, 0.2 and 2.0 micrograms/0.5 microliter) induced an immediate, but relatively short-lasting activation. Both DALA and DPEN also dose-dependently enhanced rearing; rearing was not affected by the other treatments. U50,488H (kappa agonist; 0.0186, 0.186 and 1.86 micrograms/0.5 microliter) had no effect on any aspect of motor activity. In contrast to effects on motor activity, none of the opiate agonists significantly potentiated responding for CR, although morphine infusion did tend to increase responding somewhat. In contrast, D-amphetamine (20 micrograms/0.5 microliter) did potentiate responding, as previously reported. A distinction between the effects of opiates and psychostimulants on reinforced responding is hypothesized based on differential modulation of dopamine release. These experiments demonstrate a dissociation of the effects of opiates on locomotor activity and reward-related responding.
Cunningham
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Department of Psychology, Harvard University, Cambridge, MA 02138.
Kelley
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D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D007267:Injections; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000033:anatomy & histology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects; D012201:Reward; D013238:Stereotaxic Techniques
D009294:Narcotics; D011957:Receptors, Opioid; D009020:Morphine