Pharmacological reactivity to cocaine in adult rats undernourished at perinatal age: behavioral and neurochemical correlates.
The influence of neuronal alterations induced by early undernutrition on the stimulant effect of cocaine was assessed in adult rats submitted to a protein deprivation schedule at perinatal age. To evaluate the sensitization phenomenon induced by repeated cocaine administration, different groups of control (C) and deprived (D) rats received a daily injection of cocaine (5, 10 or 15 mg/kg, i.p.) for 16 days. Behavioral parameters were assessed every two days in an open-field. Dose-response curves obtained with different doses of cocaine used revealed a shift to the left in the locomotor activity curves of D rats compared to controls. Thus, D animals showed a clear behavioral sensitization to the lower dose of cocaine, whereas this phenomenon was only observed in C rats for the higher dose used. To correlate this differential development of sensitization with neurochemical parameters, we assessed extracellular dopamine (DA) levels in nucleus accumbens (core and shell) and in the dorsal caudate-putamen, using a microdialysis technique. A challenge with cocaine in cocaine pre-exposed animals produced a different increase in DA output only in nucleus accumbens "core" of D animals. Comparable DA levels were observed in nucleus accumbens shell and in dorsal caudate-putamen of both groups. These results demonstrate that D rats had a lower threshold developing a progressive behavioral sensitization following repeated cocaine administration, as well as higher responsiveness of the nucleus accumbens (core) expressed by increased DA release.
Valdomero
Analía
A
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, Ciudad Universitaria, 5016 Córdoba, Argentina.
Isoardi
Nora A
NA
Orsingher
Otto A
OA
Cuadra
Gabriel R
GR
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004044:Dietary Proteins / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D044342:Malnutrition / Q000378:metabolism* / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule
D004044:Dietary Proteins; D003042:Cocaine; D004298:Dopamine