Individual differences in dopamine uptake in the dorsomedial striatum prior to cocaine exposure predict motivation for cocaine in male rats

Opposing Spatially Segregated Function of Endogenous GDNF-RET Signaling in Cocaine Addiction

“…Nevertheless, the data do suggest an overall reduction in endogenous dopamine in response to cocaine upon GDNF reduction, which at first sight may seem surprising given dopamine levels have been shown to positively correlate with CPP [42,68]. However, a recent study showed, in contrast to dopamine levels in the dorsomedial striatum, a negative correlation between NAc dopamine levels and active lever responding during the first day of conditioned reward extinction [16]. Together with our results, this may indicate that a modest reduction in DA predisposes one to a slower cocaine-induced CPP extinction.…”

“…Delayed CPP extinction following cocaine administration and CPP reinstatement is believed to Biomolecules 2023, 13, 761 2 of 17 model human drug-seeking behavior and substance abuse relapse [13]. Supporting this idea, stimulant-induced CPP has been observed in rodents [15][16][17], primates [18], and humans [19].…”

Hypocretin / Orexin Receptor 1 Knockdown in GABA or Dopamine Neurons in the Ventral Tegmental Area Differentially Impact Mesolimbic Dopamine and Motivation for Cocaine

“…For example, low DAT expression is associated with slower DA uptake rate [ 82 – 88 ], and reduced DAT sensitivity to cocaine [ 7 , 83 – 86 , 88 ]. Furthermore, there is evidence to suggest that low DAT expression is associated with reduced behavioral responses to psychostimulants [ 82 , 87 , 89 ], though the direction of effect varies from study to study [ 90 – 93 ]. In our studies, we did not find differences in total DAT expression with Hcrtr1 knockdown in either DA or GABA neurons suggesting that observed changes in DA transmission are not likely to be associated with DAT expression on the membrane.…”