Binge eating and psychostimulant addiction

Many of the various factors,characteristics,and variables involved in the addictive process can determine an individual’s vulnerability to develop drug addiction.Hedonic eating,based on pleasure rather than energy needs,modulates the same reward circuits,as do drugs of abuse.According to the last report of the World Health Organization,the worldwide obesity rate has more than doubled since 1980,reaching especially critical levels in children and young people,who are overexposed to high-fat,high-sugar,energy-dense foods.Over the past few decades,there has been an increase in the number of studies focused on how eating disorders can lead to the development of drug addiction and on the comorbidity that exists between the two disorders.Herein,we review the most recent research on the subject,focusing especially on animal models of binge eating disorders and drug addiction.The complex profile of patients with substance use and binge eating disorders requires an integrated response to dually diagnosed patients.Nutritional patterns should be considered an important variable in the treatment of substance use disorders,and future studies need to focus on specific treatments and interventions in individuals who show a special vulnerability to shift from one addiction to the other.

A review of psychostimulant-induced neuroadaptation in developing animals

The effects of clinically relevant doses of commonly prescribed stimulants methylphenidate （MPH）, d-am- phetamine （d-AMPH）, and dl-AMPH or mixed amphetamine salts （MAS） such as Adderall, on short- and long-term gene neuroadaptations in developing animals have not been widely investigated. In the present review, the effects of oral stimulant administration were compared with those of the subcutaneous or intra-peritoneal route. A selective set of stud- ies between 1979 and 2010, which incorporated in their design developmental period, clinically relevant doses of stimu- lants, and repeated daily doses were reviewed. These studies indicate that neuroadaptation to chronic stimulants includes blunting of stimulated immediate early gene expression, sensitivity of younger （prepubertal） brain to smaller dosages of stimulants, and the persistence of some effects, especially behavioral neuroadaptations, into adulthood. In addition, oral amphetamines （MAS） have more profound effects than does oral MPH. Further animal developmental studies are required to understand potential long-term neuroadaptations to low, daily oral doses of stimulants. Implications for clinical practice were also discussed.

Microinjection of Ghrelin into the Ventral Tegmental Area Potentiates Cocaine-Induced Conditioned Place Preference

Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to further investigate ghrelin’s role in dopamine-mediated reward, the present report examined whether pretreament with ghrelin, administered directly into the ventral tegmental area (VTA) of the midbrain, would potentiate the rewarding properties of cocaine as measured by CPP. Adult male Sprague-Dawley rats were given access to either side of the CPP chamber in order to determine initial side preferences. The rats were then restricted to either their non-preferred or preferred side over the course of conditioning which lasted for a total of 16 consecutive days. This was followed by a final test day to then reassess preference. On days where rats were confined to their non-preferred side, ghrelin (30-300 pmol) and cocaine (0.625-10 mg/kg IP) were administered immediately prior to the conditioning trial. On alternate days rats were treated with vehicle and placed into what was initially determined to be their preferred side. CPP was calculated as the difference in percentage of total time spent in the treatment-paired compartment during the post-conditioning session and the pre-conditioning session. Our results indicated that both cocaine and ghrelin elicited CPP and that ghrelin pretreatment potentiated the effect of cocaine on place preference. Overall, these findings provide additional support for the argument that ghrelin signaling within the VTA enhances the rewarding effects of psychostimulant compounds.

Effect of Chronic DL-Amphetamine Exposure on Brain Volume, Anxiogenic, Locomotor, and Social Behaviors in Male SD Rats

Research examining the long-term effects of drugs such as AdderallTM, a mixed DL-amphetamine, as a first-line treatment strategy for those diagnosed with attention deficit hyperactivity disorder (ADHD), is very much lacking. In order to address this, the present study sought to examine possible behavioral and neuroanatomical effects of chronic oral exposure to DL-amphetamine administered at a relatively low dose to the developing male Sprague Dawley rat. Animals were administered a mixture of chocolate drink and DL-amphetamine at a dose of 1.6 mg/kg for 36 days, beginning at PD 24 and ending at PD 60. Anxiety, a potential side effect of stimulant treatment, was assessed using three paradigms: The open field test (OF), the social interaction test (SI), and the elevated plus maze (EPM). The OF and SI were conducted using repeated testing over the course of five weeks. Testing occurred immediately after drug administration on a given day. The EPM was used only once on the penultimate day of treatment, before the drug was administered. Following drug treatment on PD 60, brain-to-body weight ratios were obtained. Results indicated that there were no group differences in brain-to-body weight ratios nor were differences in locomotor and social behaviors observed. However, rats treated with DL-amphetamine did show an anxiogenic response in the EPM. This was represented as a significant reduction in open arm entries. Overall our findings suggest that while chronic drug treatment fails to alter multiple measures of behavior, or reliable changes in brain volume, such treatment may impact a behavioral index of anxiety. Future research should seek to examine the implications of this heightened anxiogenic response in animals treated chronically with oral, low-dose DL-amphetamine.

Cocaine Alters the Daily Activity Patterns of Adult SD Female Rats

The effects of chronic cocaine administration on the locomotor rhythmic patterns of adult female Sprague-Dawley (SD) rats were recorded using an open-field testing assay. The animals were divided into four groups, control (saline), 3.0 mg/kg, 7.5 mg/kg, and 15.0 mg/kg i.p. cocaine group respectively. On experimental day (ED 1), all animals were treated with saline. On ED 2 to ED 7, either saline or cocaine (3.0, 7.5, or 15.0 mg/kg i.p.) was given followed by three days of no treatment (ED 8 to ED 10). On ED 11, rats were treated as they were on ED 2 to ED 7, i.e. either saline, 3.0, 7.5, or 15.0 mg/kg i.p. cocaine. The locomotor activities of rats were recorded for 23 hours daily, allowing one hour for the animal handling and injections, using open field cages with 16 infrared beams of motion detectors. Any breakages of these beams due to the movement of the animals were recorded and compiled by a computer and analyzed. It was observed that all three doses of repeated cocaine administration (3.0 mg/kg, 7.5 mg/kg, and 15.0 mg/kg i.p. cocaine) significantly alter the locomotor rhythmic activity patterns of the adult female SD rats, which suggest that repeated cocaine exposure modulates body homeostasis.

Ritalin Dose Response Effect on Medial Prefrontal Cortex and on Animal Behavior

The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC was dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects;however, most users were adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.