Novelty Seeking and Drug Addiction in Humans and Animals: From Behavior to Molecules

Abstract

Global treatment of drug addiction costs society billions of dollars annually, but current psychopharmacological therapies have not been successful at desired rates. The increasing number of individuals suffering from substance abuse has turned attention to what makes some people more vulnerable to drug addiction than others. One personality trait that stands out as a contributing factor is novelty seeking. Novelty seeking, affected by both genetic and environmental factors, is defined as the tendency to desire novel stimuli and environments. It can be measured in humans through questionnaires and in rodents using behavioral tasks. On the behavioral level, both human and rodent studies demonstrate that high novelty seeking can predict the initiation of drug use and a transition to compulsive drug use and create a propensity to relapse. These predictions are valid for several drugs of abuse, such as alcohol, nicotine, cocaine, amphetamine, and opiates. On the molecular level, both novelty seeking and addiction are modulated by the central reward system in the brain. Dopamine is the primary neurotransmitter involved in the overlapping neural substrates of both parameters. In sum, the novelty-seeking trait can be valuable for predicting individual vulnerability to drug addiction and for generating successful treatment for patients with substance abuse disorders.

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

“…Minor allele frequencies are typically higher in mouse populations than human populations, rendering possible the detection of small effect alleles. Selective breeding for behavioral phenotypes that correlate with drug‐seeking behaviors enriches and genetically fixes risk alleles . In a study with high responder and low responder rats selectively bred based on exploratory locomotion in a novel environment, seven genome‐wide significant loci accounted for approximately one‐third of total variance and two‐thirds of genetic variance selected for this trait .…”

The Association between the Level of Plasma Oxytocin and Craving among Former Heroin Users

“…Although it is as yet unclear whether oxytocin and dopamine have a direct association, accumulating evidence has suggested that oxytocin may have a positive effect on treatment for alcohol use disorders and other problematic substance abuse [16, 17]. In addition, there could exist an association between dopamine and novelty-seeking tendency [18], which could be an important issue related to addiction and oxytocin [19-21]. …”

Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants

“…As a matter of fact, we found an association between COMT rs4680 and NS in the whole sample, partially consistent with literature data that links dopaminergic transmission with this TCI dimension. In particular, it has been hypothesized that NS is modulated by the dopaminergic activity within the midbrain dopaminergic neurons (e.g., [60, 61], which in turn is regulated by the meso-cortical dopaminergic pathway (e.g., [27, 62, 63]). Thus, it could be hypothesized that the low-dopaminergic activity associated with the Val/Val genotype within the meso-cortical dopaminergic pathway leads to an upregulation of the mesolimbic pathway, which in turn determines higher NS levels.…”