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.

Keywords: Addiction; Drugs of abuse; Heritability; Molecular connections; Novelty seeking.

Figure 1

Illustration of open field arena test, one of the most commonly used behavioral paradigms to test novelty-seeking behavior in rodents. This test provides an inescapable environment in which rodents are placed in an apparatus, with the following parameters being recorded for each animal: time spent in the center versus the sides and movements against a floor grid. Because of the enclosed environment, the open field test provokes a strong fear response in rodents, as measured by elevated corticosterone concentrations. This test directly measures locomotion, which can vary independently of neophilia. As such, this test is utilized by researchers who are testing anxiety in addition to novelty-seeking behavior in rodents.

Figure 2

Illustration of hole-board test, a free-choice novelty-seeking behavioral task test for rodents. The apparatus is an enclosed box with equally spaced holes; the following behavioral parameters are measured during the test session: head dipping, nose poking, rearing, and grooming. Head dipping and nose poking represent exploratory behaviors that are independent of locomotor activity. Compared with the open field arena test (see Figure 1), the hole-board test more directly measures novelty-seeking behavior, because it has not been shown to elevate the corticosterone concentration. The hole-board test is advantageous to researchers studying novelty-seeking behavior in naïve rodents.

Figure 3

Contributing factors to drug addiction, portraying the multifaceted vulnerability to substance abuse and its relation to novelty-seeking behavior. There is no clear cause-and-effect relation between novelty-seeking behavior and drug addiction. Rather, these two phenotypes synergistically influence each other, along with an intricate network of contributing factors including age, genetic predisposition, use of addictive drugs, and environmental factors.

Figure 4

Illustration of the neurocircuitry involved in the response to rewarding stimuli, including drugs of abuse and novelty. Dopamine (DA) plays a key role in this system, through excitatory projections directly connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAc) and prefrontal cortex (PFC). Other excitatory neurotransmitters include glutamate (Ahmadi et al.), serotonin (5-HT), opioid peptides (OP), and acetylcholine (ACh). A major inhibitory neurotransmitter of this reward system is GABA, connecting the VTA, NAc, PFC, thalamus, and ventral palladium. Other brain regions implicated in the response to rewarding stimuli include the hippocampus, amygdala, raphe nuclei, striatum, and arcuate nucleus.