Dopamine is an important neuromodulator involved in reward-processing, movement control, motivational responses, and other aspects of behavior in most animals. In honey bees (Apis mellifera), the dopaminergic system has been implicated in an elaborate pheromonal communication network between individuals and in the differentiation of females into reproductive (queen) and sterile (worker) castes. Here we have identified and characterized a honey bee dopamine transporter (AmDAT) and a splice variant lacking exon 3 (AmDATΔex3). Both transcripts are present in the adult brain and antennae as well as at lower levels within larvae and ovaries. When expressed separately in the Xenopus oocyte system, AmDAT localizes to the oocyte surface whereas the splice variant is retained at an internal membrane. Oocytes expressing AmDAT exhibit a 12-fold increase in the uptake of [3H]dopamine relative to non-injected oocytes, whereas the AmDATΔex3-expressing oocytes show no change in [3H]dopamine transport. Electrophysiological measurements of AmDAT activity revealed it to be a high-affinity, low-capacity transporter of dopamine. The transporter also recognizes noradrenaline as a major substrate and tyramine as a minor substrate, but does not transport octopamine, L-Dopa, or serotonin. Dopamine transport via AmDAT is inhibited by cocaine in a reversible manner, but is unaffected by octopamine. Co-expression of AmDAT and AmDATΔex3 in oocytes results in a substantial reduction in AmDAT-mediated transport, which was also detected as a significant decrease in the level of AmDAT protein. This down-regulatory effect is not attributable to competition with AmDATΔex3 for ER ribosomes, nor to a general inhibition of the oocyte’s translational machinery. In vivo, the expression of both transcripts shows a high level of inter-individual variability. Gene-focused, ultra-deep amplicon sequencing detected methylation of the amdat locus at ten 5′-C-phosphate-G-3′ dinucleotides (CpGs), but only in 5–10% of all reads in whole brains or antennae. These observations, together with the localization of the amdat transcript to a few clusters of dopaminergic neurons, imply that amdat methylation is positively linked to its transcription. Our findings suggest that multiple cellular mechanisms, including gene splicing and epigenomic communication systems, may be adopted to increase the potential of a conserved gene to contribute to lineage-specific behavioral outcomes.
The mood disorder 'major depression' is a significant contributor to disability in society. One of the most significant determinants of an individual's risk of depression is their experience of adversities during childhood. Evidence is beginning to accumulate for a gene x environment relationship between childhood environment, including adversities, and genotype for the DRD4-exIII-VNTR. The presence of a 7rpt allele for this polymorphism has been linked to increased sensitivity of externalising behaviours, pro-social behaviour and altruism to childhood environment. A recent study has found that the sensitivity of an individual's behavioural activation system-a cortical circuit that controls motivation and reaction to reward-is protected from adversities in childhood by this 7rpt allele. In this paper, a known negative correlation between the behavioural activation system and depression led to the hypothesis that DRD4 may also play a protective role against childhood adversities in terms of the risk of depressive symptoms. However, in a representative sample of the population (n = 1,630) aged 20-24, DRD4 and childhood adversity were not found to interact in the formation of depressive symptoms (β=0.069, p=0.381).
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