Substance dependence is characterized by a group of symptoms, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). These symptoms include tolerance, withdrawal, drug consumption for alleviating withdrawal, exaggerated consumption beyond original intention, failure to reduce drug consumption, expending a considerable amount of time obtaining or recovering from the substance’s effects, disregard of basic aspects of life (for example, family), and maintenance of drug consumption, despite facing adverse consequences. The nucleus accumbens (NAc) is a brain structure located in the basal forebrain of vertebrates, and it has been the target of addictive drugs. Different neurotransmitter systems at the level of the NAc circuitry have been linked to the different problems of drug addiction, like compulsive use and relapse. The glutamate system has been linked mainly to relapse after drug-seeking extinction. The dopamine system has been linked mainly to compulsive drug use. The glutamate homeostasis hypothesis centers around the dynamics of synaptic and extrasynaptic levels of glutamate, and their impact on circuitry from the prefrontal cortex (PFC) to the NAc. After repetitive drug use, deregulation of this homeostasis increases the release of glutamate from the PFC to the NAc during drug relapse. Glial cells also play a fundamental role in this hypothesis; glial cells shape the interactions between the PFC and the NAc by means of altering glutamate levels in synaptic and extrasynaptic spaces. On the other hand, cocaine self-administration and withdrawal increases the surface expression of subunit glutamate receptor 1 (GluA1) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors at the level of the NAc. Also, cocaine self-administration and withdrawal induce the formation of subunit glutamate receptor 2 (GluA2), lacking the Ca2+-permeable AMPA receptors (CP-AMPARs) at the level of the NAc. Antagonism of the CP-AMPARs reduces cravings. It is necessary to pursue further exploration of the AMPA receptor subunit composition and variations at the level of the NAc for a better understanding of glutamatergic plastic changes. It is known that cocaine and morphine are able to induce changes in dendritic spine morphology by modifying actin cycling. These changes include an initial increase in spine head diameter and increases in AMPA receptor expression, followed by a second stage of spine head diameter retraction and reduction of the AMPA receptors’ expression in spines. Besides glutamate and dopamine, other factors, like brain-derived neurotrophic factor (BDNF), can influence NAc activity and induce changes in dendritic spine density. BDNF also induces drug-related behaviors like self-administration and relapse. Neither apoptosis nor neurogenesis plays a relevant role in the neurobiological processes subjacent to cocaine addiction in adults (rodent or human). Different therapeutic drugs like N-acetylcysteine (NAC), modafinil, acamprosate, and topira...

The current work is targeted to review the risks of gabapentin misuse, its potential interactions with other drugs, side effects and use contraindications. This review consists of a total of 99 biographical references (from the year 1983 to 2016). A publication search of PubMed was performed from January 1983 to December 2016. It included animal studies, clinical studies, case studies and reviews related to gabapentin misuse, potential interactions, side effects and use contraindications. The search terms were gabapentin, anticonvulsant and antiepileptic. In general, it seems that gabapentin has risks of being misused based on the increased level of prescriptions, related fatalities, recreational misuse and higher doses of self-administration. The main reasons for gabapentin misuse are as follows: getting high, alleviating opioid withdrawal symptoms and potentiating methadone effects. Some of the main substances that interact with gabapentin are morphine, caffeine, losartan, ethacrynic acid, phenytoin, mefloquine and magnesium oxide. Some of the side effects caused by gabapentin are teratogenicity, hypoventilation, respiratory failure and myopathy. Finally, reports in general contraindicate the use of gabapentin in conditions such as myasthenia gravis and myoclonus.

Dopamine activates five different receptor subtypes and a complex array of intracellular signaling pathways. Rhes is a striatally-expressed GTP-binding protein involved in dopamine signaling. Here we have used mutant mice to test whether Rhes is involved in D1 and D2 dopamine receptor-mediated behaviors. Rhes was not necessary for the expression of normal D1/D2 receptor synergism, as measured by apomorphine-induced stereotypy. The stereotypic responses to D1/D2 co-stimulation and to D2 stimulation alone were significantly increased in mice lacking Rhes, but D1 receptormediated grooming was reduced in these mice. These results suggest that Rhes is normally inhibitory to behaviors induced by D1/D2 receptor co-stimulation and by D2 receptor stimulation alone. However, Rhes appears to facilitate the D1-specific behavior of grooming.

Pain is an intricate phenomenon composed of not only sensory-discriminative aspects but also of emotional, cognitive, motivational, and affective components. There has been ample evidence for the existence of an extensive cortical network associated with pain processing over the last few decades. This network includes the anterior cingulate cortex, forebrain, insular cortex, ventrolateral orbital cortex, somatosensory cortex, occipital cortex, retrosplenial cortex, motor cortex, and prefrontal cortex. Diverse neurotransmitters participate in the cortical circuits associated with pain processing, including glutamate, gamma-aminobutyric acid, dopamine, and opioids. This work examines recent rodent studies about cortical modulation of pain, mainly at a molecular level.

Relapse to cocaine seeking is associated with potentiated excitatory synapses in nucleus accumbens. ␣ 2 ␦-1 is an auxiliary subunit of voltage-gated calcium channels that affects calcium-channel trafficking and kinetics, initiates extracellular signaling cascades, and promotes excitatory synaptogenesis. Previous data demonstrate that repeated exposure to alcohol, nicotine, methamphetamine, and morphine upregulates ␣ 2 ␦-1 in reward-related brain regions, but it was unclear whether this alteration generalized to cocaine. Here, we show that ␣ 2 ␦-1 protein was increased in nucleus accumbens after cocaine self-administration and extinction compared with saline controls. Furthermore, the endogenous ligand thrombospondin-1, responsible for the synaptogenic properties of the ␣ 2 ␦-1 receptor, was likewise elevated. Using whole-cell patch-clamp recordings of EPSCs in nucleus accumbens, we demonstrated that gabapentin, a specific ␣ 2 ␦-1 antagonist, preferentially reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation in slices from cocaine-experienced rats compared with controls. In vivo, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin's effects on drug seeking were not due to a general depression of spontaneous or cocaine-induced locomotor activity. Moreover, gabapentin had no effect on reinstatement of sucrose seeking. These data indicate that ␣ 2 ␦-1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy.