**1. Introduction**

The use of psychoactive drugs that induce dependence (including psychostimulants (such as cocaine, methamphetamine, etc.), opioids (heroin, methadone, etc.), cannabinoids, tobacco, and alcohol, among others) is widely extended in the first world countries [1, 2]. The widespread drug use entails a main socioeconomic burden, because drug use is associated to antisocial behavior and delinquency, violence and accidents, social exclusion, physical and psychiatric illnesses, and even disability and death [1, 2]. In this regard, it is worth mentioning that a recent global study identified alcohol as the leading risk factor for premature death in the population aged 15–49 years [1]. Considering the severity of the drug use problem, the World

Health Organization currently destines efforts for substance abuse management in order to improve both treatment and prevention programs (https://www.who.int/ substance\_abuse/publications/drugs/en/).

Nevertheless, while drug use entails significant risks, regular usage of drugs is not a synonym of suffering a drug addiction disorder. Drug addiction (or substance use disorder—SUD) is a chronic disorder with a high relapse rate, in which the person "loses control" over drug intake despite the negative consequences on their daily life and even against the desire to remain abstinent [3]. Drug addiction may only be experienced by a subgroup of more "vulnerable" individuals that get in contact with drugs. Specifically, approximately 11% of people that use drugs would develop a SUD, meaning an uncontrollable and harmful drug use pattern that may need treatment [2]. Therefore, the scientific community has invested in investigating those factors or mechanisms that cause and explain the onset and maintenance of a SUD. As the deleterious impact of addictive drugs on the brain—the organ that controls behavior became evident, addiction has been considered as a "brain disease" [4]. The current "brain disease" model of addiction has important implications for SUD prevention and treatment, since medical interventions that regulate brain functioning (e.g., pharmacotherapy) may be valid for addiction, and persons with SUDs may benefit for public treatment policies reserved to other medical illnesses, while the social stigma is attenuated since drug addiction is a medical condition instead of a voluntary choice or an hedonistic act [4]. However, this model is not exempt of criticism [5, 6], partially because the relevance of social and psychological factors is diminished in favor of the biological elements, and freeing the person from responsibility underestimates the importance of the personal willpower and motivation toward therapeutic change.

Setting this controversy aside, there is a consensus in that drug addiction, being a "brain disease" or not, certainly involves a neurobiological brain dysfunction that affects behavior. Brain morphological alterations in persons using different drug types (such as alcohol, cannabis, cocaine, methamphetamine, heroin, or tobacco) have been consistently reported even at the macrostructural level, usually involving significant gray and/or white matter shrinkage [7–13]. Moreover, functional neuroimage techniques reveal that connectivity among brain regions is also dysregulated [14]. It is important to note that the aberrant brain structure and function associated to drug addiction most likely results from a combination of (biological) brain features that exist *previous to* drug use as vulnerability factors, with the neuroadaptations that are *induced by* the drug itself (**Figure 1A**). Solid evidence has been provided in both ways (reviewed in [15]). On the one hand, individual differences in the form of stable personality traits such as impulsivity, elevated anxiety, risk-taking, and sensation seeking that are assumed to entail a particular biological and brain basis [16, 17] may predispose to engage in both drug use and addiction. On the other hand, brain and behavioral abnormalities often correlate with drug use patterns (i.e., the amount of drug consumed and/or the number of years using the drug) and may be completely or partially recovered by protracted drug abstinence [7, 8, 11, 13, 15, 18], suggesting that they were directly induced by the continuous action of the drug. Notably, preclinical studies in laboratory animals (that allow the exposure to the drug to be controlled by the experimenter) have confirmed both evidences. Individual traits in rodents (e.g., increased impulsivity) predict their subsequently exacerbated response to drugs compared to rodents that do not show this feature (e.g., [19, 20]); and both brain and behavioral alterations are experimentally induced by administering drugs to naïve animals (e.g., [21–23]).

Therefore, while it is difficult—especially for clinical research—to elucidate whether the observed behavioral and brain features are cause or consequence of drug use, both drug vulnerability factors and drug-induced brain effects are likely *Aberrant Brain Neuroplasticity and Function in Drug Addiction: A Focus on Learning-Related… DOI: http://dx.doi.org/10.5772/intechopen.85280*

#### **Figure 1.**

*(A) The "drug addiction cycle." Numerous factors intervene in the vulnerability for drugs, including a "vulnerable brain." Drug consumption induces widespread brain neuroadaptations that, in vulnerable individuals, would be addiction-like behavioral alterations that are likely to promote further drug use, aggravating its effects. (B) A non-exhaustive schematic representation of the brain structures and connections involved the brain circuit of learning, reward, and motivated behavior. A maladaptive functioning of this circuit supports the etiology and maintenance of drug addiction. Brain structures are colored on the basis of their main neurochemical content. The dashed line represents the "spiraling" nigrostriatal connections. Abbreviations: Acb, accumbens; ACTH, acetylcholine; BLA, basolateral amygdala; Dstr, dorsal striatum; GABA, γ-aminobutyric acid; Hipp, hippocampus; PFC, prefrontal cortex; Sep, septum; SMC, sensorimotor cortex; VP, ventral pallidum; VTA, ventral tegmental area.*

to coexist and be interrelated. In the worst case scenario, a "vulnerable" brain is exposed to the drug, triggering an exacerbated response to the substance that increases the amount of drug subsequently consumed, thus also increasing the potential drug-induced harm (**Figure 1A**). Without the intent of underestimating the notable importance of psychological, social, economic, and environmental factors in the etiology and maintenance of drug addiction, this chapter will focus on the neurobiological component. In particular, we will review that the integrity of key brain regions that are normally involved in control of reward, planning,

learning, and motivated behavior is compromised in drug addiction to favor uncontrollable drug intake as well as other behavioral symptoms. Specifically, we will focus on the mesolimbic system, the dorsal striatum, and the limbic regions as key components of the "brain addiction circuit."
