Archival ReportStriatal Dopamine Responses to Intranasal Cocaine Self-Administration in Humans
Section snippets
Subjects
Ten nondependent cocaine users (aged 23.7 ± 2.8; two women, eight men; see Table 1) were recruited from the community through advertisements in local newspapers. For all subjects, the primary and preferred route of self-administration was intranasal. All were free of current or past substance dependence, as determined by a semistructured clinical interview for DSM-IV diagnoses (10). Six of the 10 participants were current light smokers with a score of less than 3 on the Fagerstrom Test for
Plasma Cocaine
Plasma concentrations of cocaine differed significantly between the test sessions as reflected by a Test × Time interaction [F(3,21) = 35.3, p ≤ .0001]. Plasma cocaine levels peaked at 45 min post–cocaine self-administration, midscan (mean ± SD: 149 ± 44 ng/mL). Cocaine was not detected in plasma on the drug-free (placebo) test day or on the baseline measure before cocaine self-administration.
PET Aata: Analyses of t Maps
A voxelwise analysis revealed a significant decrease in [11C]raclopride BP values on the test with
Discussion
We investigated the effect of intranasal cocaine self-administration on striatal DA responses in nondependent cocaine users. There were two primary novel findings. First, cocaine self-administration, compared with placebo powder, decreased [11C]raclopride binding levels and did so preferentially within the ventral limbic striatum and postcommissural putamen. Second, individual differences in the magnitude of the cocaine-induced [11C]raclopride response in the ventral striatum were predicted by
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Conditioned inhibition of amphetamine sensitization
2022, Neurobiology of Learning and MemoryCitation Excerpt :Conditioned inhibition could explain why detoxified volunteers with a cocaine use disorder have reduced striatal DA responses following a psychostimulant challenge (Volkow et al., 1997); the laboratory setting is not associated with drugs and thus functions as a conditioned inhibitor (Vezina and Leyton, 2009). Supporting this idea, if cocaine users are allowed to prepare and take the drug in the lab as they would typically, then striatal DA responses show evidence of sensitization as a function of past drug use (Cox et al., 2009), but not when drug-taking paraphernalia and other drug-taking cues are absent (Casey et al., 2014). Interestingly, drug-related cues provided in a cocaine cue video did not enable striatal DA responding in cocaine misusers, suggesting that these may not be as effective as those involved in the actual drug self-administration (Volkow et al., 2014).
PET imaging of neurotransmission using direct parametric reconstruction
2020, NeuroImageCitation Excerpt :For instance, PET used in conjunction with 11C-raclopride, a D2–like receptor antagonist radioligand, can detect transient changes in endogenous striatal dopamine concentration following administration of amphetamine (Breier et al., 1997) or a motor planning task (Alpert et al., 2003). This imaging technique has been used for more than two decades to probe the neurochemical underpinnings of cognitive and motivational functions in normal and neuropathological conditions, including substance abuse (Volkow et al., 1997; Cox et al., 2009; Busto et al., 2009; Martinez et al., 2005), schizophrenia (Breier et al., 1997; Abi-Dargham et al., 1998), Tourette’s syndrome (Singer et al., 2002; Wong et al., 2008) and Parkinson’s disease (Lidstone et al., 2010; Tedroff et al., 1996; Fuente-Fernández et al., 2001; Steeves et al., 2009). The competition between radioligand and neurotransmitter for binding to receptor sites is the fundamental principle underpinning the technique.
Non-pharmacological factors that determine drug use and addiction
2020, Neuroscience and Biobehavioral ReviewsDrug-induced stress responses and addiction risk and relapse
2019, Neurobiology of StressCitation Excerpt :There have been decades of focus on mesolimbic striatal dopaminergic pathways as critical for the reinforcing effects of psychoactive drugs. While striatal adaptation may drive compulsive drug motivation, other positron emission tomography (PET) evidence indicates that psychoactive drug-stimulated increases in cortisol is highly correlated with dopamine release in the striatum (Booij et al., 2016; Cox et al., 2009; Wand et al., 2007) and drug-induced cortisol increases are associated with the subjective intoxication in healthy volunteers (Oswald et al., 2005). Similarly, psychological stress provocation in healthy volunteers has also been shown to increase dopamine transmission in the striatum and the PFC (Nagano-Saito et al., 2013; Pruessner et al., 2004), and cortisol responses to psychosocial stressors predict reward after amphetamine administration (Hamidovic et al., 2010).
Reward processing and mood-related symptoms: An RDoC and translational neuroscience perspective
2017, Journal of Affective Disorders