Alterations in Striatal Circuits Underlying Addiction-Like Behaviors

Abstract

Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

The Role of Adenosine Receptors in Psychostimulant Addiction

“…The negative emotional stage of withdrawal may be due to activation of the amygdala with norepinephrine, dynorphin and corticotropin-releasing factor. The third stage, craving, depends on the prefrontal cortex, amygdala and hippocampus, and glutamate is the major neurotransmitter involved (reviewed in Kelley and Berridge, 2002 ; Koob and Volkow, 2010 ; Kim et al, 2017 ; Figure 1 ). The NAc acts as a hub of convergence from the different regions, and it has been considered a key element in the neuronal circuitry of drug addiction.…”

Increased Absolute Glutamate Concentrations and Glutamate-to-Creatine Ratios in Patients With Methamphetamine Use Disorders

“…Drug addiction is a severe mental illness characterized by compulsive drug abuse despite the potential undesirable consequences. Previous studies have indicated that the use of psychoactive stimulants may lead to changes in a wide range of neurological circuits and physiological processes ( 38 ). Psychostimulants play a significant role in promoting the structural plasticity of reward circuits in the brain ( 39 ).…”

Interactions of Glutamatergic Neurotransmission and Brain-Derived Neurotrophic Factor in the Regulation of Behaviors after Nicotine Administration

“…The dorsal striatum is comprised of the caudate nucleus and putamen (CPu), and the ventral striatum of the nucleus accumbens (NAc) [8,24]. The CPu receives dopaminergic inputs from the substantia nigra pars compacta in the midbrain and glutamatergic inputs mainly from the somatosensory cortex [24,25]. On the other hand, the NAc receives dopaminergic inputs from the ventral tegmental area (VTA) in the midbrain and glutamatergic inputs from the prefrontal cortex (PFC) [25].…”