Repeated Cocaine Exposure Effects on Catecholamines in the Nucleus Accumbens Septi of Periadolescent Animals

AbstractBackground:In previous studies, we have observed that specificN-methyl-d-aspartic acid (NMDA) antagonists and non-NMDA antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the plus maze test in rats. In the present study, the effect of intracanalicular blockade of NMDA receptors using dizocilpine in the plus maze was studied in male rats bilaterally cannulated NAS.Methods:Rats were divided into five groups that received either 1 μL injections of saline or dizocilpine (MK-801, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine) in different doses (0.5, 1, 2, or 4 μg) 15 min before testing.Results:Time spent in the open arm increased under dizocilpine treatment with the two higher doses (2 and 4 μg, p<0.05), extreme arrivals were increased by the three higher doses (1 μg, p<0.05; 2 and 4 μg, p<0.01), and open arm entries by the three higher doses (1, 2, and 4 μg, p<0.05). A dose-effect relationship was observed in all cases.Conclusions:We conclude that dizocilpine-glutamatergic blockade in the accumbens lead to an anxiolytic-like effect and a behavioral disinhibition related to an increase in some motoric parameters, showing specific behavioral patterns.

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Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

Journal of Neurophysiology ◽

10.1152/jn.00413.2010 ◽

2010 ◽

Vol 104 (2) ◽

pp. 922-931 ◽

Cited By ~ 32

Author(s):

Nii A. Addy ◽

David P. Daberkow ◽

Jeremy N. Ford ◽

Paul A. Garris ◽

R. Mark Wightman

Keyword(s):

Nucleus Accumbens ◽

Dopamine Release ◽

Cocaine Exposure ◽

Sprague Dawley ◽

Nucleus Accumbens Core ◽

Fast Scan Cyclic Voltammetry ◽

Uptake Inhibition ◽

Sprague Dawley Rats ◽

Dopamine Signaling

Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine pre-exposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent Km of 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects.

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