Ghrelin receptor alters dopamine signaling

Appetite accomplice: Ghrelin receptor alters dopamine signaling -- ScienceDaily

• Dopamine signaling in the hypothalamus is linked with feeding behavior, and mutations in DRD2 that attenuate dopamine signaling are associated with obesity in humans.
  
• When mice were treated with a molecule (cabergoline) that selectively activates DRD2, they exhibited anorexia.
  

Mechanical ventilation can cause brain damage through dopamine induced apoptosis in hippocampus

Triggers Hippocampal Apoptosis by Vagal and Dopaminergic Pathways
-Adrián González-López, Inés López-Alonso, et al.
American Journal of Respiratory and Critical Care Medicine, Volume 188, Issue 6, 15 September 2013.
Researchers find why ICU ventilation can cause brain damage
-Medical News Today, 26 September 2013.

Excerpts:

• Patients who have been mechanically ventilated in intensive care units have long been known to suffer some form of mental impairment as a result. Now, researchers have uncovered a molecular mechanism that may explain why this happens.
• In comparison with the control mice, the mice on ventilation showed evidence of neuronal cell death in the hippocampus as a result of apoptosis - the process of programmed cell death. The research team discovered that the apoptosis process was caused by dopamine-induced suppression of Akt - a molecule that usually prevents neuronal apoptosis.
• The research team discovered that the apoptosis process was caused by dopamine-induced suppression of Akt - a molecule that usually prevents neuronal apoptosis.

Dopamine And Sleep Regulation

Dopamine And Sleep Regulation

• "These results are interesting as they demonstrate a mechanism in which dopamine, normally increased at times of stimulation, can directly inhibit production and release of a molecule, melatonin, that induces drowsiness and prepares the body for sleep..."

Drug-resistant hyperprolactinemia

MEN1 frequently involves pituitary disease. One study found pituitary disease occurred in 42% of MEN1 patients.⁽¹⁾ Depending on the specific type of pituitary disorder, treatment may include the surgical removal of an adenoma, the use of hormones or drugs to normalize pituitary function, or radiotherapy.

A prolactinoma, for example, is a non-cancerous pituitary tumor that produces the hormone prolactin; it's the most common form of pituitary tumor.⁽²⁾ Prolactinomas tend to cause hyperprolactinemia, abnormally high blood levels of prolactin. This can cause a variety of symptoms, including interfering with normal ovulatory function in women.

Normally, prolactin-producing cells are down-regulated, or inhibited, by dopamine signals from the hypothalamus.⁽³⁾ Therefore, hyperprolactinemia often is treated by dopamine agonists, usually Cabergoline or Bromocriptine.

Cabergoline usually is more effective than Bromocriptine at normalizing prolactin levels and restoring gonadal function.⁽⁴⁾ Yet it is not always successful in lowering prolactin to normal levels.

One particular patient, "P", was found to have hyperprolactinemia which then prompted an MRI scan and diagnosis of a pituitary adenoma. Treatment with Cabergoline was started. Within four months, the adenoma shrank and was no longer detectable via MRI, and P's prolactin level dropped to normal levels. But not for long. The prolactin level began to rise, and P's doctor responded with increasing dosage of Cabergoline. This went on for eight years, with Caborgoline dosage of up to 2.5mg/wk and prolactin levels typically about 50-100 mg/dL. When Cabergoline was discontinued, the prolactin would shoot up to about 180, and when Cabergoline was resumed, prolactin would reduce but not normalize. Periodic MRIs suggested possible empty sella syndrome and no sign of adenoma.

P's treatment subsequently was switched to Bromocriptine for a year, but her prolactin did not respond as well as it did to Cabergoline, and so Cabergoline was resumed.

What is there to do for a patient whose hyperprolactinemia does not respond sufficiently to dopamine agonist therapy, and who does not exhibit an operable adenoma?
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⁽¹⁾ Bruno Vergès, et al. Pituitary Disease in MEN Type 1 (MEN1): Data from the France-Belgium MEN1 Multicenter Study. The Journal of Clinical Endocrinology & Metabolism February 1, 2002 vol. 87 no. 2, 457-465.
⁽²⁾ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001377/
⁽³⁾ http://en.wikipedia.org/wiki/Dopamine#Regulating_prolactin_secretion
⁽⁴⁾ Webster, et al. A Comparison of Cabergoline and Bromocriptine in the Treatment of Hyperprolactinemic Amenorrhea. N Engl J Med 1994; 331:904-909