Alcohol consumption receptors

Findings from animal studies suggest that neuropeptide Y (NPY) may be associated with ethanol consumption. NPY-deficient mice have increased alcohol consumption (Thiele et al. 1998), an effect that is mediated by the Y1 and Y2 receptors (Pandey et al. 2003 Thiele et al. 2000, 2002). It has been suggested that NPY Y1 agonists and Y2 antagonists may have promise in the treatment of alcoholism (Cowen et al. 2004). 

Thiele TE, Koh MT, Pedrazzini T Voluntary alcohol consumption is controlled via the neuropeptide YYl receptor. J Neurosci 22 RC208, 2002... 

Naltrexone (ReVia). Naltrexone is another medication that has specific FDA approval for the treatment of alcohol use disorders. It is used as an interference therapy. Naltrexone blocks opioid receptors in the brain and is believed to reduce alcohol-induced euphoria. The absence of pleasurable effects associated with alcohol consumption should plausibly lead to a decrease in the behavior of drinking alcohol. Evidence to date has demonstrated that recovering alcoholics treated with naltrexone have fewer days of drinking and longer periods of sobriety between relapses. 

Thiele TE, Marsh DJ, Ste Marie L, Bernstein IL, Palmiter RD (1998) Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 396 366-369 Thiele TE, Koh MT, Pedrazzini T (2002) Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor. J Neurosci 22 RC208 Thorsell A, Rimondini R, Heilig M (2002) Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats. Neurosci Lett 332 1-4 Timmusk T, Palm K, Metsis M (1993) Multiple promoter direct tissue-specific expression of rat BDNF gene. Neuron 10 475-489... 

Naltrexone, a relatively long-acting opioid receptor antagonist, blocks the effects at -opioid receptors (see Chapter 31). Studies in experimental animals first suggested a link between alcohol consumption and opioids. Injection of small amounts of opioids was followed by an increase in alcohol drinking, whereas administration of opioid antagonists inhibited self-administration of alcohol. 

Recall from our discussion of cocaine and amphetamines that the body responds to the long-term abuse of these stimulants by creating more depressant receptor sites. Likewise, the body recognizes the excessive inhibitory actions produced by alcohol and tries to recover by increasing the number of synaptic receptor sites that lead to nerve excitation. A tolerance for alcohol therefore develops. To receive the same inhibitory effect, the drinker is forced to drink more, which induces the body to create even more excitable synaptic receptor sites. Eventually, an excess of these excitatory receptor sites leads to perpetual body tremors, which can be subdued either by more drinking or, with greater difficulty, by a long-term cessation of alcohol consumption. 

Oral baclofen has also been used to reduce alcohol consumption in people who are chronic alcohol abusers.21,22 Apparently, relatively low doses of baclofen can reduce the cravings and desire for alcohol consumption via the effects of this drug on CNS GABA receptors.21 Future studies will help clarify the role of this drug in treating chronic alcoholism. 

In 1951, disulfiram was the first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence other than detoxification. Disulfiram inhibits a key enzyme, aldehyde dehydrogenase, involved in breakdown of ethyl alcohol. After drinking, the alcohol-disulfiram reaction produces excess blood levels of acetaldehyde, which is toxic in that it produces facial flushing, tachycardia, hypotension, nausea and vomiting, and physical discomfort. Opioid receptors antagonists, such as naloxone and naltrexone (see Chapter 47) that block opioid receptors have been found to decrease alcohol consumption (Cornish et al 2004). 

Crabbe JC, Phillips TJ, Feller DJ, et al. Elevated alcohol consumption in null mutant mice lacking 5-HT1B serotonin receptors. Nat Genet 1996 14(1) 98-101. 

Wang H, Yu M, Ochani M, Amelia CA, Tanovic M, Susaria S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 2003 421 384-388. Das UN. Alcohol consumption and risk of dementia. Lancet 2002 360 490. 

The DRD4 gene has a variable number tandem repeat (VNTR) located in exon 3, with the common alleles of two, four, and seven repeats [65]. The seven repeat appears to be the critical allele relevant to pharmacotherapy and alcohol consumption. Functionally, the DRD4 seven tandem repeat allele codes for a dopamine receptor D4 that blunts intracellular forskolin-stimulated cyclic AMP (cAMP) response to dopamine relative to the receptor encoded by the two and four tandem repeat alleles [66]. 

Rouvinen-Lagerstrom N, Lahti J, Alho H, Kovanen L, Aalto M, Partonen T, Silander K, Sinclair D, Raikkonen K, Eriksson JG, Palotie A, Koskinen S, Saarikoski ST (2013) mu-Opioid receptor gene (OPRM1) polymorphism A118G lack of association in Finnish populations with alcohol dependence or alcohol consumption. Alcohol Alcohol 48 519-525... 

Hungund BL, Szakall I, Adam A, Basavarajappa BS, Vadasz C (2003) Cannabinoid CBi receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens. J Neurochem 84 698-704... 

Vasopressin (antidinretic hormone) is a nonapeptide that controls resorption of water by distal tubules of the kidney to regulate the osmotic pressure of blood. It functions to conserve body water by reducing the output of urine, and thus it is known as an antidiuretic. Vasopressin is synthesized in the supraoptic nucleus of the hypothalamus where it is bound to a neurophysin protein carrier, packaged in granules, and delivered by intracellular transport to nerve terminals in the posterior pituitary. Vasopressin bound to neurophysin is released from the granules in response to increased extracellular osmolarity sensed by hypothalamic osmoreceptors, signaling by atrial stretch receptors or after a rise in angiotensin n levels. Its secretion is increased by dehydration or stress and decreased after alcohol consumption. 

Important in helping their son or daughter remain or become sub stance-free is understanding the nature of adolescence well enough to recognize the developmental risks that make adolescents emotionally receptive to drug and alcohol consumption, and then to parent against those risk receptors. 

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