Serotonin function in pathological gambling: blunted growth hormone response to Sumatriptan

Abstract

Pathological gambling is a disruptive behaviour and an important public health concern that is classified as an impulse control disorder, and is also conceptualized as a prototype of 'behavioural addiction'. Its phenomenology cannot be reduced to a single neurobiological dysfunction; instead, it has been conceived as a complex chain of events in which the serotonergic system (5-HT) has often been suggested as one of the most prominent involved. Acute administration of Sumatriptan, a selective 5-HT(1B/1D) agonist, has been used to investigate the functional responsivity of 5-HT(1B/1D) receptors in alcoholics, resulting in a blunted growth hormone response. These findings have been interpreted as being due to the down-regulation of these receptors. However, previous studies could not rule out the possibility that the changes in receptor function were induced by chronic substance exposure. Twenty-two pathological gamblers and 19 healthy control subjects were evaluated in response to double-blind administration of both a single dose of oral Sumatriptan (100 mg) and of placebo in a crossover design. All participants were screened to ensure that they were negative for lifetime alcohol and drug addiction, and had been free of substance abuse for at least 6 months. Outcome measures included growth hormone, prolactin, gambling severity, mood, craving and 'high' change scales. A blunted growth hormone response was observed in pathological gamblers compared with healthy controls after Sumatriptan administration. No statistically significant differences were found for prolactin or behavioural measures, except for an increase in anxiety over time in pathological gamblers. These results, together with those obtained in our previous serotoninergic challenge study, document the presence of a serotonergic dysfunction in pathological gamblers similar to that reported in alcoholics.

Similarities and differences between pathological gambling and substance use disorders: a focus on impulsivity and compulsivity

“…Pallanti et al (2010) reported those with PG had lower baseline ventral striatal glucose metabolism and higher levels in the dorsal striatum than healthy controls. In a different study (Linnet et al 2011), PG participants did not differ significantly from healthy controls in D2-like receptor availability in the ventral striatum at baseline.…”

“…Differences in activity in PG associated with PD may localize specifically to ventral components of striatum (Cilia et al 2010; Frosini et al 2010; O'Sullivan et al 2011; Steeves et al 2009). Limited available evidence suggests hyperactivity in the dorsal striatum in PG (Habib and Dixon 2010; Pallanti et al 2010). Likewise, dorsal striatal hyperactivity has also been observed in substance dependence (e.g., cocaine; Volkow et al 2006).…”

“…In contrast, control subjects tend to report aversive responses to mCPP (DeCaria et al 1998; Pallanti et al 2006). Blunted growth hormone response to sumatriptan, a selective 5-HT1B receptor agonist, has also been observed in PG (Pallanti et al 2010), whereas increased growth hormone release has been seen in control subjects (Herdman et al 1994). …”

“…Not only is SUD research likely to be illustrative for PG, the study of PG also may also inform our understanding of and future investigations into substance addictions. PG presents an opportunity to study addictive behaviors without necessarily being confounded by neurotoxicity associated with acute or chronic substance use (Lawrence et al 2009b; Pallanti et al 2010; Verdejo-Garcia et al 2008). …”

Treatment of Gambling Disorders

“…Evidence from multiple lines of research suggest alterations in serotonergic functioning among individuals with GD (e.g., [19]); however, findings from clinical trials thus far suggest limited efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of GD (for a review see [8]). To date, four different SSRIs have been studied: fluvoxamine [20; Class III; 21; Class I; 22; Class I; 23; Class II], sertraline [24; Class I], escitalopram [25; Class II; 26; Class II] and paroxetine [27; Class I; 28; Class I].…”