Nucleus accumbens dopaminergic medication of fixed interval schedule-controlled behavior and its modulation by low-level lead exposure.
To examine the assertion that changes in nucleus accumbens (NAC) dopamine (DA) activity serve as a mechanism of lead (Pb)-induced disruption of fixed interval (FI) schedule-controlled behavior, the effects of intra-NAC administration of the irreversible DA antagonist EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihyroquinoline) and of dopamine itself on FI performance were compared in rats that had been chronically exposed to 0, 50 or 500 ppm Pb acetate in drinking water from weaning. Pb exposure per se (500 ppm), as in past studies, increased FI response rates, primarily by shortening interresponse times. Although DA, which produced rate-dependent effects, increased FI rates at low doses in the 0 and 50 ppm groups, it did so by decreasing postreinforcement pause times. All DA doses decreased rates in the 500 ppm group. In contrast, the DA antagonist EEDQ suppressed FI response rates, effects that were not strongly rate dependent, by increasing both postreinforcement pause values and mean interresponse times. Pb exposure (500 ppm) delayed the recovery of response rates to control levels at the highest EEDQ dose, raising the possibility of a delay in receptor production rate. Collectively, these data suggest that NAC DA activity may be an important modulator of FI response rates. Enhanced NAC DA activity may contribute to Pb-associated increases in FI rates and may underlie the differential response of control and 500 ppm Pb-treated groups to intra-NAC DA administration. The different processes by which DA and Pb increase FI rates, however, suggests that additional mechanisms are operative in the case of Pb.
Cory-Slechta
D A
DA
Department of Neurobiology and Anatomy, University of Rochester Medical School, Rochester, New York 14642, USA. slechta@envmed.rochester.edu
O'Mara
D J
DJ
Brockel
B J
BJ
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000502:physiology*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D012055:Reinforcement Schedule; D013997:Time Factors
D018492:Dopamine Antagonists; D011804:Quinolines; D007854:Lead; C000470:EEDQ; D004298:Dopamine