A glutamate-dopamine interaction in the persistent enhanced response to amphetamine in nucleus accumbens core but not shell following a single restraint stress.
The administration of psychostimulant drugs or stress can elicit a sensitized response to the stimulating and reinforcing properties of the drug. We previously demonstrated that a single restraint stress session enhanced d-amphetamine (d-AMPH)-induced locomotion the day after the stress session, which lasted up to 8 days. The present experiments were designed to identify the contribution of major dopamine (DA) brain areas in the short- and long-lasting enhancement of d-AMPH-induced locomotion following a single stress, and to test the involvement of N-methyl-D-aspartate (NMDA) receptors in that phenomena. To achieve our goal, 24 h and 8 days after a 2-h restraint stress session either with or without a NMDA receptor blockade, we measured locomotor activity and DA overflow in nucleus accumbens (NAcc) core and shell and caudate putamen (CPu) following a d-AMPH injection (0.5 mg/kg i.p.). The stimulant effect of d-AMPH on DA overflow was enhanced in all nuclei at 24 h after a single stress, while at 8 days the enhanced responsiveness was maintained only in the NAcc core. When the rats were administered with MK-801 (0.1 mg/kg i.p.) 30 min before restraint stress, the d-AMPH-induced enhancement on locomotor activity and DA neurotransmission was prevented in all studied brain areas at both times. These findings show that a glutamate-dopamine link is underlying the short- and long- term d-AMPH-induced enhancement on DA and locomotor activity following stress. The persistent glutamate-dependent DA enhancement in NAcc core highlights the relevance of this region in the long-term proactive effects of stress on vulnerability to drug abuse.
Pacchioni
Alejandra M
AM
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Cador
Martine
M
Bregonzio
Claudia
C
Cancela
Liliana M
LM
D000661:Amphetamine / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000503:physiopathology*
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000661:Amphetamine; D004298:Dopamine