Impact of Ghrelin and Cocaine on Intracranial Self-Stimulation in Rats
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Ghrelin (GHR) is a 28-amino acid peptide that is secreted in the peripheral and central nervous systems and correlates with hunger. GHR is the only gut hormone known to stimulate food intake. Psychostimulant drugs, such as cocaine (COC), induce locomotion and augment reward-seeking behavior. Recent studies have examined the effects of GHR on locomotion and report an augmenting effect when combined with COC. In the present study, we examine the effects of systemic injections of COC, GHR, and a pairing of both on rate-frequency curves, maximal response rate, and threshold (the frequency that produces 50% of the maximal response rate) obtained during intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB). In this task, rats press a lever to deliver electrical pulses to their own brain via an implanted electrode. Rats are run in 75 minute sessions, consisting of five 15-minute passes; during each pass, the intensity (in ?amps) is kept constant, while the frequency of stimulation is lowered each minute from 141 Hz to 28 Hz (decreased in 0.05 log units). Each rat runs multiple trials on separate days and is injected with either vehicle (0.5 ml saline), COC (0, 2.5, and 5.0 mg/kg), GHR (5.0, 10.0, and 30.0 nMol/rat), or a combination of GHR and COC (10.0 nMol/rat GHR and 2.5 mg/kg COC). GHR produced a significant dose-dependent effect, where the rate-frequency curves shifted to the right, maximal response rate and 50% response rate decreased, and threshold increased. COC produced the opposite effect. A combination of GHR and COC shifted the rate-frequency curves to the right and caused a significant increase in threshold. Dopamine (DA) plays a critical role in reinforcement and is found in neurological reward pathways, such as the ventral tegmental area (VTA) and the nucleus accumbens (NA). Since GHR receptors exist in these two areas, some researchers suggest that there may be a common pathway shared by the rewarding aspects of food and psychostimulants leading to obesity and drug abuse, respectively. The present results suggest that in some circumstances, GHR may inhibit already active reinforcement systems.
Kniffin, Tracey C (2010). Impact of Ghrelin and Cocaine on Intracranial Self-Stimulation in Rats. Honors and Undergraduate Research. Available electronically from