In this Issue-December 1st| Volume 64, ISSUE 11, P917-918, December 01, 2008

In this Issue-December 1st

        Animal Models of Reward Behavior

        A new class of drugs that acts by preventing the breakdown of anandamide, a cannabis-like substance made by the body, may not be associated with a significant abuse liability. This conclusion is supported by a study by Justinova et al. (pages 930–937). These authors characterized the effects of inhibiting the enzyme fatty acid amide hydrolase (FAAH) that metabolizes anandamide on reward in monkeys. They demonstrated that an FAAH inhibitor, URB597, elevates endogenous anandamide levels throughout the monkey brain. They also found that URB597 lacks reinforcing properties in monkeys, distinguishing it from classical cannabinoids and other directly acting cannabinoid agonists.
        DeltaFosB, a molecular “switch” implicated in drug addiction, may also play a role in the rewarding effects of fatty foods. Teegarden et al. (pages 941–950) utilized a mouse model of heightened reward sensitivity to identify some molecular mechanisms that might contribute to the rewarding effects of fatty foods. They studied mice that were engineered to overexpress DeltaFosB. These addiction-prone animals showed low expression levels for a group of genes implicated in dopamine-related signal transduction. When these animals were fed high fat diets, the abnormal pattern of gene expression “normalized.” When the fatty diet was withdrawn, these animals showed signs of withdrawal.

        Genetics of Nicotine Dependence

        Grucza et al. (pages 922–929) report the surprising finding that a variant of the nicotinic receptor gene CHRNA5, which was previously implicated as a risk factor for nicotine dependence, exhibits a protective association with cocaine dependence. This finding was detected in a sample ascertained for cocaine dependence, and replicated in a second sample ascertained for alcoholism. These results suggest that the influence of some genes on addiction may vary markedly according to a drug's mechanism of action.
        Li et al. (pages 951–957) conducted a case-control sample to evaluate whether there is gene-gene interaction among the four genes known to affect nicotine dependence. Using an algorithm, they found highly significant gene-gene interactions for the gene pairs of CHRNA4 and CHRNB2, CHRNA4 and NTRK2, CHRNB2 and NTRK2, and BDNF and NTRK2 and significant interaction between CHRNA4 and BDNF. This study provides an example of how traditional analysis may fail to identify important risk genes and that the use of a validated detection strategy for interactions is warranted.

        Hippocampal Neurogenesis Altered by Methamphetamine Self-Administration

        Mandyam et al. (pages 958–965) evaluated the effects of intermittent and daily self-administration of methamphetamine on the hippocampal functioning of adult rats. They found that intermittent access to methamphetamine initially stimulated the development of new nerve cells, while daily access decreased the numbers of new nerve cells. These data suggest that even modest daily doses of methamphetamine could contribute to pathological changes in the hippocampus.

        The Impact of Drugs of Abuse on Brain Activation

        Borgwardt et al. (pages 966–973) used functional MRI in healthy volunteers to measure the effects of the two main psychoactive constituents of cannabis, delta-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol (CBD), on brain activation during response inhibition. The findings suggest that the cognitive impairments associated with cannabis intoxication are related to the influence of Δ-9-THC, but not CBD.
        Despite progress, individuals seeking treatment for cocaine abuse and dependence still show high rates of relapse. Brewer et al. (pages 998–1004) tested the hypothesis that brain activation during a cognitive control task would predict outcome measures in cocaine-dependent individuals undergoing treatment. The authors found that the pattern of cortical activation during a response inhibition task was related to treatment outcome. For example, abstinence was associated with activity in a circuit involving the ventral prefrontal cortex, while the percentage of drug-free urines was associated with activity in the striatum.

        Evaluating Addictions Through the Opioid System

        Nielsen et al. (pages 974–981) evaluated the effects of a novel delta opioid receptor blocker, SoRI9409, on high- and low-ethanol–consuming rats. They discovered that SoRI9409 was three times more effective and selective at reducing ethanol consumption in high-ethanol-consuming rats as compared with naltrexone or naltrindole. This compound may offer a new strategy for the treatment of alcohol use disorders.
        There is increasing evidence that brain kappa-opioid receptors (KORs) play an important role in the regulation of mood states. Using the intracranial self-stimulation test, Tomasiewicz et al. (pages 982–988) demonstrate that acute administration of a KOR agonist in rats blocks the rewarding effects of cocaine. This finding raises the possibility that KOR agonists might ameliorate symptoms of conditions characterized by increased motivation and hyperfunction of brain reward systems, such as stimulant intoxication and mania.
        The endogenous opioid system influences the rewarding and addictive effects of drugs of abuse. Racz et al. (pages 989–997) have investigated the role of the opioid peptides enkephalin and beta-endorphin using genetically modified mouse models, followed by a genetic study in alcoholic patients. Their findings provide evidence for an important function of beta-endorphin in the regulation of alcohol consumption.

        Odor Sensitivity in ADHD

        In many neuropsychiatric disorders, olfactory function is impaired. In a study investigating children and adolescents with attention-deficit/hyperactivity disorder (ADHD), Romanos et al. (pages 938–940) found improved olfactory sensitivity compared to healthy controls. Treating children with ADHD with methylphenidate normalized olfactory function. Improved odor sensitivity might be a specific feature of ADHD and might be useful for differential diagnosis and assessment of treatment effects.

        Biological Disturbances in Anorexia Nervosa

        Ghrelin and obestatin modulate food intake; therefore, changes in these hormones might play a role in the pathophysiology of anorexia nervosa (AN). Monteleone et al. (pages 1005–1008) found that vagal stimulation during food ingestion induced an enhanced secretion of ghrelin and a more robust drop of obestatin in underweight AN women. Since ghrelin stimulates whereas obestatin reduces food ingestion, these changes might have pathophysiological implications for the aberrant eating behavior of AN patients.
        Serotonin receptor functioning has previously been shown to be altered in AN. Galusca et al. (pages 1009–1013) evaluated [18F]MPPF binding via positron emission tomography and eating-related traits in AN and control subjects. They found increased [18F]MPPF binding in both current and recovered AN patients, supporting the hypothesis that serotonergic modulation of frontotemporal regions might play a role in AN.