Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys.
ABSTRACT The present study examined the time course of alterations in levels of dopamine transporter (DAT) binding sites that accompany cocaine self-administration using quantitative in vitro receptor autoradiography with [(3)H]WIN 35,428. The density of dopamine transporter binding sites in the striatum of rhesus monkeys with 5 d, 3.3 months, or 1.5 years of cocaine self-administration experience was compared with DAT levels in cocaine-naive control monkeys. Animals in the long-term (1.5 years) exposure group self-administered cocaine at 0.03 mg/kg per injection, whereas the initial (5 d) and chronic (3.3 months) treatment groups were each divided into lower dose (0.03 mg/kg per injection) and higher dose (0.3 mg/kg per injection) groups. Initial cocaine exposure led to moderate decreases in [(3)H]WIN 35,428 binding sites, with significant changes in the dorsolateral caudate (-25%) and central putamen (-19%) at the lower dose. Longer exposure, in contrast, resulted in elevated levels of striatal binding sites. The increases were most pronounced in the ventral striatum at the level of the nucleus accumbens shell. At the lower dose of the chronic phase, for example, significant increases of 21-42% were measured at the caudal level of the ventral caudate, ventral putamen, olfactory tubercle, and accumbens core and shell. Systematic variation of cocaine dose and drug exposure time demonstrated the importance of these factors in determining the intensity of increased DAT levels. With self-administration of higher doses especially, increases were more intense and included dorsal portions of the striatum so that every region at the caudal level exhibited a significant increase in DAT binding sites (20-54%). The similarity of these findings to previous studies in human cocaine addicts strongly suggest that the increased density of dopamine transporters observed in studies of human drug abusers are the result of the neurobiological effects of cocaine, ruling out confounds such as polydrug abuse, preexisting differences in DAT levels, or comorbid psychiatric conditions.
- SourceAvailable from: Thomas J R Beveridge
Dataset: Beveridge11 Cocaine+mGluR23
Dataset: Porrino07 Shifting Target
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ABSTRACT: Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.Nutrients 11/2014; 6(11):5153-5183. · 3.15 Impact Factor