Striatal dopamine D1-type receptor availability: no difference from control but association with cortical thickness in methamphetamine users

Abstract

Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on postmortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1 receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity. Thus, both receptor subtypes may contribute to methamphetamine-induced alterations in cortical morphology and behavior. In this study, 21 methamphetamine-dependent subjects and 23 healthy controls participated in positron emission tomography and structural magnetic resonance imaging for assessment of striatal D1- and D2-type receptor availability and cortical gray-matter thickness, respectively. Although D2-type receptor availability (BPND) was lower in the methamphetamine group, as shown previously, the groups did not differ in D1-type BPND. In the methamphetamine group, mean cortical gray-matter thickness was negatively associated with cumulative methamphetamine use and craving for the drug. Striatal D1-type but not D2-type BPND was negatively associated with global mean cortical gray-matter thickness in the methamphetamine group, but no association was found between gray-matter thickness and BPND for either dopamine-receptor subtype in the control group. These results suggest a role of striatal D1-type receptors in cortical adaptation to chronic methamphetamine use.

Cognitive deficit in methamphetamine users relative to childhood academic performance: link to cortical thickness

“…Consistent with a previous examination of a subsample of participants in the current study (of which 70% of participants overlap, [17]), cortical thickness did not differ between methamphetamine users and healthy control subjects. Memory deficit scores, however, were related to overall cortical thickness in methamphetamine users, less thickness being associated with more pronounced memory deficits.…”

“…Smaller cortical thickness may thus function as a risk factor for the development of subsequent memory problems or other clinically relevant phenomena that could hamper treatment responsiveness. Notably, smaller cortical thickness in methamphetamine users has also been associated with stronger craving for the drug [17].…”

“…The participants were 41 healthy control and 37 methamphetamine-dependent subjects who were not seeking treatment. Data on cognitive performance of these subjects have not been previously published; group differences in cortical thickness were previously examined from a subset of the subjects (~70%) [17]. The participants were recruited using Internet and local newspaper advertisements, and they received monetary compensation in return for maintaining abstinence from drugs and completing research procedures.…”

CYP2D6 genotype may moderate measures of brain structure in methamphetamine users

“…Therefore, relative to poor metabolizers, extensive metabolizers may be exposed to an exaggerated phasic dopaminergic response to methamphetamine. Interestingly, striatal D1‐type dopamine receptor availability is negatively correlated with whole brain cortical thickness in methamphetamine users, consistent with the view that phasic dopamine release produces cortical neurotoxicity 51 . Thus, dopaminergic action may contribute to the moderating effect of CYP2D6 on cortical thickness.…”

Gray-matter structure in long-term abstinent methamphetamine users

“…However, the altered regions accepted only part of the dopaminergic projections from either the ventral tegmental area or the substantia nigra pars compacta, which implicates that these particular alternations depend less on where the dopaminergic projection comes [5], but more on, for example, the density of dopamine receptors, of this particular or relevant locations. It has been proposed that dopamine D1 receptors are major modulators of synaptic plasticity in the frontal cortex [44], additionally, previous studies have evidenced that midbrain D2/D3 [45] and striatal D1 [46] receptors modulate gray-matter adaption in chronic methamphetamine users.…”