Fentanyl-induced conditional place preference: lack of associated conditional neurochemical events

Abstract

Three experiments were performed to determine if stimuli previously paired with the reinforcing effects of fentanyl elicit changes in the activity of dopaminergic neurons that are similar to the unconditional effects of the drug. Experiment 1 characterized the unconditional effects of fentanyl (0.04 mg/kg SC) on neurochemical indices of dopaminergic activity in rats. Both acute and repeated fentanyl injections (five injections administered at 48-h intervals) increased the concentrations of the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) within the striatum (STR), nucleus accumbens (NAS), and olfactory tubercle (OT). Acute injections elicited a greater increase in metabolite concentrations in the NAS than in the STR, suggesting that there are regional differences in the sensitivity of dopaminergic neurons to fentanyl. In experiments 2 and 3, fentanyl (five injections; 0.04 mg/kg SC) was paired with environmental stimuli using a place preference conditioning paradigm. The fentanyl-paired stimuli failed to elicit conditional changes in DOPAC or HVA concentrations within the STR, NAS, or OT even though rats exhibited a preference for the drug-paired compartment of the shuttle box. These results indicate that the secondary reinforcing effects of stimuli previously paired with fentanyl may not reflect the ability of these stimuli to elicit measurable changes in the activity of mesolimbic or nigrostriatal dopaminergic neurons.