Strain differences between Lewis and Fischer 344 rats in the modulation of dopaminergic receptors after morphine self-administration and during extinction.
The Lewis (LEW) and Fischer 344 (F344) rat strains have been used as a model to study genetic vulnerability to drug addiction and they differ in their dopaminergic systems. We have studied the variation in the D1-like and D2-like receptors in distinct brain regions of LEW and F344 rats that self-administered morphine (1 mg/kg) for 15 days and also after different extinction periods (3, 7 and 15 days). Under basal conditions, binding to D1-like receptors in the olfactory tubercle and substantia nigra, and to D2-like receptors in the Pyriform cortex and hippocampal-CA1 was lower in LEW rats than in F344 rats. Conversely, the LEW rats exhibited stronger D2-like binding in the caudate-putamen. In most brain regions there was a decrease in D1-like binding in LEW rats after self-administration while the F344 animals displayed an increment. Additionally, D2 receptors of LEW rats were down-regulated after self-administration in the caudate-putamen and in the nucleus accumbens (shell and core divisions). Binding to D1-like receptors increased in both strains in the early phases of extinction, while in the later stages a differential regulation was observed between both strains. During the early phases of extinction only F344 rats showed alterations in D2-like receptor binding, however in the latter phases a specific modulation occurred in both strains. These differences in basal D1-like and D2-like receptor binding, and their differential modulation after self-administration and during extinction, may be reflected in the greater vulnerability to opiate addiction shown by LEW strain.
Psychobiology Department, School of Psychology, UNED, C/Juan del Rosal no. 10, 28040 Madrid, Spain.
Pilar
P
Sánchez-Cardoso
Alejandro
A
Higuera-Matas
Sonsoles
S
Martín
Miguel
M
Miguéns
Nuria
N
Del Olmo
Carmen
C
García-Lecumberri
Emilio
E
Ambrosio
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011954:Receptors, Dopamine / Q000378:metabolism*; D012646:Self Administration / Q000379:methods; D013045:Species Specificity; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D018492:Dopamine Antagonists; D009294:Narcotics; D011954:Receptors, Dopamine; D014316:Tritium; D009020:Morphine