Opioids in the hypothalamus control dopamine and acetylcholine levels in the nucleus accumbens

Abstract: The experimental question is whether hypothalamic opioids, known to stimulate consummatory behavior, control a link to the nucleus accumbens (NAc). It was hypothesized that opioids injected in the hypothalamic paraventricular nucleus (PVN) alter the balance of dopamine (DA) and acetylcholine (ACh) in the NAc in a manner that fosters appetite for food or ethanol. Rats were implanted with two guide shafts, one in the NAc to measure extracellular DA and ACh by microdialysis and the other in the PVN for microinjection of opioid μ- and δ-agonists, an antagonist, or saline vehicle. The compounds tested were morphine, the μ-receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin (DAMGO), the δ-receptor agonist d-Ala-Gly-Phe-Met-NH2 (DALA), and the opioid antagonist naloxone methiodide (m-naloxone). Morphine in the PVN increased the release of accumbens DA (+41%) and decreased ACh (−35%). Consistent with this, the opioid antagonist m-naloxone decreased DA (−24%) and increased ACh (+19%). In terms of receptor involvement, DAMGO dose-dependently increased DA to up to 209% of baseline. Simultaneously, ACh levels were markedly decreased to 55% of baseline. The agonist DALA produced a smaller but significant, 34% increase in DA, without affecting ACh. In contrast, control injections of saline had no significant effect. These results demonstrate that μ- and δ-opioids in the PVN contribute to the control of accumbens DA and ACh release and suggest that this circuit from the PVN to the NAc may be one of the mechanisms underlying opiate-induced ingestive behavior as well as naltrexone therapy for overeating and alcoholism. [Copyright &y& Elsevier]