PRECLINICAL STUDY: Correlation between serum ghrelin levels and cocaine-seeking behaviour triggered by cocaine-associated conditioned stimuli in rats


Michela Tessari, Department of Neuropsychopharmacology, Centre of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline S.p.A., Via A. Fleming 4, 37135 Verona, Italy. E-mail:


Ghrelin is a brain–gut peptide with growth hormone-releasing and appetite-inducing activities. A growing body of evidence suggests that ghrelin may affect the central reward system and modulate the activity of the mesolimbic system. Recent clinical studies also showed a significant positive correlation between plasma ghrelin levels and craving in alcoholics. Accordingly, the present study investigated the potential role of serum ghrelin levels in the reinstatement of cocaine-seeking behaviour triggered by cocaine-associated cues. In addition, serum corticosterone levels were determined in the light of evidence suggesting that corticosterone plays a modulatory role in cocaine-seeking behaviour. Male Lister Hooded rats under a restricted diet regime were first trained to intravenously self-administer cocaine under a fixed ratio-1 schedule of reinforcement. Conditioned stimuli (CS: tone and cue-light on for 5 seconds) were presented contingently with cocaine delivery. Once a stable baseline of cocaine self-administration was observed, lever presses were extinguished to less than 30% of baseline rates by removing both cocaine and CS. Reinstatement of responding was then induced by re-exposure to cocaine-associated CS. Blood samples for the enzyme immunoassay determination of serum ghrelin and the radioimmunoassay determination of serum corticosterone levels were collected 30 minutes before the beginning of reinstatement sessions. Rats significantly reinstated their responding when exposed to CS. A positive and significant correlation was observed between ghrelin levels (= 0.64; P < 0.05), but not corticosterone (= 0.37; NS), and the increased active lever presses only in animals exposed to CS. These findings suggest a potential role of ghrelin in the modulation of cue-triggered reinstatement of cocaine-seeking behaviour.