RT Journal Article
SR Electronic
T1 Heterogeneous subregional binding patterns of 3H-WIN 35,428 and 3H-GBR 12,935 are differentially regulated by chronic cocaine self- administration
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2966
OP 2979
DO 10.1523/JNEUROSCI.14-05-02966.1994
VO 14
IS 5
A1 JM Wilson
A1 JN Nobrega
A1 ME Carroll
A1 HB Niznik
A1 K Shannak
A1 ST Lac
A1 ZB Pristupa
A1 LM Dixon
A1 SJ Kish
YR 1994
UL http://www.jneurosci.org/content/14/5/2966.abstract
AB We examined the influence of chronic cocaine exposure, in an unlimited access self-administration paradigm, on density of the dopamine transporter (3H-WIN 35,428 and 3H-GBR 12,935 binding) and concentration of monoamine (dopamine, serotonin, noradrenaline and metabolites) neurotransmitters in rat brain. In normal rodent striatum 3H-WIN 35,428 and 3H-GBR 12,935 binding to the dopamine transporter, although generally similar, showed different subregional rostrocaudal and mediolateral gradients, suggesting that the two ligands might bind to different subtypes or states of the dopamine transporter. Following chronic, unlimited access cocaine self-administration, binding of 3H- WIN 35,428 was significantly elevated in whole nucleus accumbens (+69%, p < 0.001) and striatum (+65%, p < 0.001) on the last day of cocaine exposure (“on-cocaine group”); whereas in the 3 week withdrawn animals (“cocaine-withdrawn group”), levels were either normal (striatum) or reduced (-30%, p < 0.05, nucleus accumbens). Although similar changes in 3H-GBR 12,935 binding were observed, this dopamine transporter ligand showed a smaller and highly subregionally dependent increase in binding in striatal subdivision of the on-cocaine group, but a more marked binding reduction in the cocaine-withdrawn animals. As compared with the controls, mean dopamine levels were reduced in striatum (-15%, p < 0.05) of the on-cocaine group and in nucleus accumbens (-40%, p < 0.05) of the cocaine-withdrawn group. These data provide additional support to the hypothesis that some of the long-term effects of cocaine exposure (drug craving, depression) could be consequent to reduced nucleus accumbens dopamine function. Our data also suggest that dopamine transporter concentration, and perhaps function, might undergo up- or downregulation, either as a direct effect of cocaine, or indirectly as part of a homeostatic response to altered synaptic dopamine levels, and therefore might participate in the neuronal events underlying cocaine-induced behavioral changes.