Involvement of alpha-melanocyte stimulating hormone (alpha-MSH) in differential ethanol exposure and withdrawal related depression in rat: neuroanatomical-behavioral correlates.
We investigated the involvement of alpha-melanocyte stimulating hormone (alpha-MSH) following acute, chronic and withdrawal treatments of ethanol with reference to depression. The degree of depression was evaluated using Porsolt's forced swim test. While intracerebroventricular (i.c.v.) alpha-MSH (100-400 ng/rat) dose-dependently increased the immobility, opposite response was observed following administration of selective MC4 receptor antagonist HS014 (0.01-0.07 ng/rat, i.c.v.). The anti-immobility effect of acute ethanol (1-2 g/kg), injected via intra-peritoneal route (i.p.), was suppressed by central administration of alpha-MSH (100 ng/rat, i.c.v.), but was enhanced following pretreatment with HS014 (0.01 ng/rat, i.c.v.). Chronic ethanol resulted in increased immobility time, while further augmentation in immobility was noticed following ethanol withdrawal. However, concomitant HS014 (0.01 ng/rat, i.c.v.) treatment prevented tolerance as well as attenuated enhanced immobility in ethanol-withdrawn rats. Acute administration of HS014 (0.01-0.03 ng/rat, i.c.v.), at 24h post-withdrawal time point, also antagonized the ethanol withdrawal immobility in rats. The profile of alpha-MSH-immunoreactivity in the paraventricular (PVN), arcuate (ARC), paraventricular thalamic (PVT), dorsomedial hypothalamic-dorsal (DMNd) and -ventral (DMNv) nuclei, lateral hypothalamus (LH) and central nucleus of amygdala (CeA) was investigated with immunocytochemistry. Acute ethanol significantly reduced the alpha-MSH-immunoreactivity in the cells and fibers of ARC, and fibers in the PVN, DMNd, DMNv and CeA. While chronic ethanol treatment significantly increased the alpha-MSH-immunoreactivity as compared to the pair-fed control group, further augmentation was noticed following 24 h ethanol withdrawal. However, the alpha-MSH-immunoreactive profile in the PVT and LH did not respond. alpha-MSH in discrete areas may play a role in ethanol-induced antidepressant-like response and withdrawal-induced depression.
Kokare
Dadasaheb M
DM
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur, 440 033, India.
Singru
Praful S
PS
Dandekar
Manoj P
MP
Chopde
Chandrabhan T
CT
Subhedar
Nishikant K
NK
D000437:Alcoholism / Q000378:metabolism / Q000523:psychology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003863:Depression / Q000209:etiology / Q000378:metabolism*; D004334:Drug Administration Schedule; D000431:Ethanol / Q000494:pharmacology*; D046353:Immobility Response, Tonic / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000378:metabolism; D014018:Tissue Distribution; D000521:alpha-MSH / Q000008:administration & dosage / Q000187:drug effects / Q000378:metabolism*
D000928:Antidepressive Agents; D002492:Central Nervous System Depressants; D044105:Receptor, Melanocortin, Type 4; D000431:Ethanol; D000521:alpha-MSH