Glutamate and aspartate levels in the nucleus accumbens during cocaine self-administration and extinction: a time course microdialysis study.
BACKGROUND
Accumbal excitatory amino acid (EAA) transmission has been implicated in cocaine addiction. However, the time course effects of extinction of cocaine self-administration on EAAs are unknown.


OBJECTIVE
The objective of this study was to define the time course of cocaine self-administration and extinction effects on glutamate and aspartate levels in the nucleus accumbens.


METHODS
Rats were trained to self-administer cocaine for 20 days, and the levels of extracellular glutamate and aspartate were measured by in vivo microdialysis both during cocaine self-administration and after a priming cocaine injection at different time points after extinction (1, 5, or 10 days). A food-reinforced control group was also included in this study. Furthermore, the effect of acute i.v. cocaine administration (0, 1, 2, or 4 mg/kg) on glutamate and aspartate levels was also evaluated.


RESULTS
At any of the dose tested, acute i.v. cocaine did not affect the levels of glutamate or aspartate in the Nacc. In contrast, glutamate levels were reduced in animals trained to self-administer cocaine, although they augmented substantially during a subsequent session of cocaine self-administration, and similar changes were not observed in food-reinforced controls. After 1 or 5, but not after 10 days of extinction, the glutamate levels were also reduced, and the ability of i.v. cocaine priming injections to increase glutamate levels followed a similar time course. These effects were specific, as aspartate levels were not affected by any administration protocol.


CONCLUSIONS
These data suggest that glutamatergic transmission could be involved in the maintenance of cocaine self-administration and in the early phases of abstinence.
Miguéns
M
M
Departamento de Psicobiología, Facultad de Psicología, UNED, C/ Juan del Rosal no. 10, 28040 Madrid, Spain.
Del Olmo
N
N
Higuera-Matas
A
A
Torres
I
I
García-Lecumberri
C
C
Ambrosio
E
E
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects*; D045604:Extracellular Fluid / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012646:Self Administration / Q000379:methods; D013997:Time Factors
D001224:Aspartic Acid; D018698:Glutamic Acid; D003042:Cocaine