AbstractBackgroundNeuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is... Show moreAbstractBackgroundNeuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use.MethodsIn this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine.ResultsRegression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively.ConclusionThese findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders. Show less
The mechanisms that control thought and action vary with the fluctuating and dynamic nature of both internal physiological states and external environmental constraints. Psychoactive drugs have the... Show moreThe mechanisms that control thought and action vary with the fluctuating and dynamic nature of both internal physiological states and external environmental constraints. Psychoactive drugs have the ability to alter mood state or behavior by acting directly on these mechanisms. The alteration of cognitive processes is a core deficit in drug abuse that leads to a failure in regulating behavior. This thesis investigates whether the abuse of stimulant drugs like khat or cocaine somehow impact the processes that coordinate and combine information from different cognitive systems: cognitive control. In addition, we review the behavioral and physiological effects of the natural psychomotor stimulants khat and the cathinone-derived designer drug mephedrone. Show less
The objective of the research described in this thesis was to demonstrate the role of gene-environment interactions in the emergence of individual differences in cocaine use. For this purpose we... Show moreThe objective of the research described in this thesis was to demonstrate the role of gene-environment interactions in the emergence of individual differences in cocaine use. For this purpose we used two inbred mouse strains, the C57Bl/6 (C57) and DBA/2 (DBA), which are known to differ in drug-intake and to be differentially sensitive to several stressors. We studied the impact of early life experiences (long-term influence) as well as a later life psychosocial stressor (short-term influence) on adult drug intake behavior in these two mouse strains. To study the impact of the early life environment, we manipulated the maternal environment of the mice by fostering them with non-related mother strains showing either high or low pup-oriented behaviour. The late life experience consisted of a short-lasting period of group housing in adulthood. Cocaine self-administration in mice with a C57 background was not affected by either changes in postnatal maternal environment or a short group housing experience in adulthood, while these same experiences did affect mice with a DBA background. As a first step towards the biological mechanisms underlying this gene-environment interaction we found that vasopressin was differentially regulated in the extended amygdala of the DBA mice. Show less
Not everyone who experiments with cocaine acquires compulsive drug use. The mechanism underlying this individual difference in susceptibility to addiction is poorly understood. Recent studies have... Show moreNot everyone who experiments with cocaine acquires compulsive drug use. The mechanism underlying this individual difference in susceptibility to addiction is poorly understood. Recent studies have identified genes and adverse life events (stress) as risk factors. The objective of this thesis is to investigate the contribution of the adrenal stress hormones glucocorticoids and epinephrine to the psychostimulant effects of cocaine in the inbred DBA/2 and C57BL/6 mouse strains. Behavioural sensitisation, measured as an enhanced locomotor response to repeated cocaine exposure, was used as a model for the long-term neural adaptations underlying aspects of drug addiction. The results demonstrate that adrenal hormones play a critical role in cocaine sensitivity, which depends on genetic background because surgical removal of the adrenals (__adrenalectomy__) prevented cocaine sensitisation in DBA/2, but not C57BL/6 mice. The impact of genetic background was further emphasised by strain-specific changes in the midbrain dopamine system that mediates the rewarding effects of drugs. The effects of adrenalectomy could only be fully reversed by co-administration of glucocorticoids and epinephrine. These findings show that, depending on genetic background, adrenal stress hormones are important risk factors for vulnerability to cocaine, suggesting that pharmacological intervention in stress hormone action has therapeutic potential in drug addiction. Show less
