No abstract

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 (r = 0.64; P < 0.05), but not corticosterone (r = 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.

Ghrelin (GHR) is an orexigenic gut peptide that interacts with brain ghrelin receptors (GHR-Rs) to promote food intake. Recent research suggests that GHR acts as a modulator of motivated behavior, suggesting a direct influence of GHR on brain reinforcement circuits. In the present studies, we investigated the role of GHR and GHR-Rs in brain reinforcement function. Pharmacological Magnetic Resonance Imaging was used to spatially-resolve the functional activation produced by systemic administration of an orexigenic GHR dose. The imaging data revealed a focal activation of a network of subcortical structures that comprise brain reinforcement circuits – ventral tegmental area, lateral hypothalamus and nucleus accumbens. We next analyzed whether brain reinforcement circuits require functional GHR-Rs. To this purpose, wild type (WT) or mutant rats sustaining ENU-induced knockout of GHR-Rs (GHR-R null rats) were implanted with stimulating electrodes aimed at the lateral hypothalamus, shaped to respond for intracranial self-stimulation (ICSS) and then tested using a rate-frequency procedure to examine ICSS response patterns. WT rats were readily shaped using stimulation intensities of 75 uA, whereas GHR-R null rats required 300 uA for ICSS shaping. No differences in rate-frequency curves were noted for WT rats at 75 uA and GHR-R null rats at 300 uA. When current intensity was lowered to 100 uA, GHR-R null rats did not respond for ICSS. Taken collectively, these data suggest that systemic GHR can activate mesolimbic dopaminergic areas, and highlight a facilitative role of GHR-Rs on the activity of brain reinforcement systems.

No abstract

To test the hypothesis that the lung represents a source of interleukin (IL)-6 in human immunodeficiency virus type 1 (HIV-1)-positive subjects, alveolar macrophages (AM) obtained from the bronchoalveolar lavage (BAL) fluid of 10 HIV-1-positive patients were investigated for the expression of IL-6 mRNA and the ability to release IL-6. The presence of IL-6 in BAL fluid was also investigated. It has been demonstrated that freshly recovered AM from HIV-1-positive patients show a strong IL-6 mRNA signal. The message for IL-6 increases following culture with LPS. Supernatants obtained from AM cultured in medium alone contain high amounts of IL-6; the values are three to four times higher following culture with LPS. IL-6 has also been detected in the BAL fluid from 5 of 8 HIV-1-positive patients. Results of immunoblotting analysis were consistent with those given above. These findings suggest that the lung represents a source of IL-6 production in HIV-1-infected subjects with lung disorders.