Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [¹¹C]raclopride study in humans

Abstract

The results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

“…The outcomes suggest that 5-HT plays differential roles over cocaine-seeking versus cocaine reward (above), and between drug-seeking generated in the absence or presence of cocaine itself (Table 1). This pattern of observations is mirrored in humans as tryptophan depletion suppressed cue-evoked craving in the absence of cocaine administration (Satel, et al, 1995) and augmented cocaine-primed craving (Cox, et al, 2011) suggesting that cue- and cocaine-primed craving are under the regulation of 5-HT neurotransmission. A defining characteristic of these studies is whether cocaine is present at time of study, however, it is necessary to consider the small number of studies and that the neuroadaptations associated with repeated cocaine exposure are superimposed upon the overlapping, widespread changes of central 5-HT levels evinced by these 5-HT manipulations (see 8.…”

“…There are no published reports of which we are aware that have evaluated the influence of 5-HT manipulations on cocaine self-administration in humans directly. However, in self-report analyses, fluoxetine suppressed cocaine-induced subjective effects and drug “liking” (Walsh, et al, 1994) while tryptophan depletion augmented cocaine-induced drug “wanting” (Cox, et al, 2011) but suppressed the “high” induced by intravenous cocaine (Aronson, et al, 1995). These few results in humans must be interpreted with caution as it is unclear whether self-report of drug-induced state reflects sensitivity to the reinforcing effects of the drug (Matuskey, et al, 2012), however they provide support to the general concept that 5-HT may regulate the reward value of cocaine.…”

Altitude May Contribute to Regional Variation in Methamphetamine Use in the United States: A Population Database Study

“…These phenomena are also closely associated with alterations of DA and 5-HT levels in the brain 57,58. MA use among youth has a consistent relationship with depression, and suicide likely contributes to increased morbidity and mortality among MA users 59.…”

Serotonin 5-HT2Receptor Interactions with Dopamine Function: Implications for Therapeutics in Cocaine Use Disorder

“…In humans, pretreatment with a selective SERT inhibitor decreases ratings of cocaine's positive effects (Walsh et al, 1994). In contrast, lowered 5-HT activity via tryptophan depletion increases cocaine craving and cocaine-induced DA release as measured by reductions of [ 11 C]raclopride binding with PET imaging (Cox et al, 2011). Together, these studies suggest that 5-HT can negatively modulate the abuserelated effects of cocaine.…”