If the entire materia medica at our disposal were limited to the choice and use of only one drug, I am sure that a great many, if not the majority, of us would choose opium ([Macht, 1915][1]).

### A. Early History

Opium is the dried milky juice of the unripe seed capsule of the poppy, the Papaver

Opioids, Reward and Addiction: An Encounter of Biology, Psychology, and Medicine

Consumption of ethanol solution is potentiated by morphine and attenuated by naloxone persistently across repeated daily administrations.

1. Alcohol is one of the most widely used recreational drugs, but also one of the most widely abused, causing vast economic, social and personal damage. 2. Several animal models are available to study the reinforcing mechanisms that are the basis of the abuse liability of ethanol. Innate differences in opioid or dopamine neurotransmission may enhance the abuse liability of ethanol, as indicated by animal and human studies. 3. Opioid antagonists have been shown to be effective, both experimentally and clinically, in decreasing ethanol consumption, presumably since ethanol induces the release of endogenous opioid peptides in vivo. However, ethanol may also stimulate the formation of opiate-like compounds, which could interact with opioid (or dopamine) receptors. Ethanol may cause changes in neurotransmission mediated via opioid receptors that determines whether alcohol abuse is more or less likely. 4. Ethanol appears to facilitate dopamine release by increasing opioidergic activity, disinhibiting dopaminergic neurons (by inhibition of GABAergic neurotransmission) via mu-opioid receptors in the ventral tegmental area (VTA) and delta-opioid receptors in the nucleus accumbens (NAcc). The effects of ethanol would be antagonised by presynaptic kappa-opioid receptors present on dopaminergic terminals in the NAcc. 5. Mesolimbic dopamine release induced by ethanol consumption seems to indicate ethanol-related stimuli are important, focussing attention on and enabling learning of the stimuli. However, studies indicate that there are redundant pathways, and neural pathways 'downstream' of the mesolimbic dopamine system, which also enable the reinforcing properties of ethanol to be mediated.

The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption.

Summary
This paper presents a new model of alcohol drinking based on the observation that alcohol drinking often occurs following uncontrollable events. The psychological concepts of compensatory opponent process systems and learned helplessness give new insights into the biobehavioral response of organisms to environmental events and how these events can affect alcohol drinking. Finally by integrating these behavioral data with biochemical data which demonstrate that alcohol stimulates endorphin activity, it is proposed that organisms drink alcohol to reduce deficiencies in endorphin activity.

Uncontrollable events and alcohol drinking.

Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system.

Two groups of 14 male Sprague-Dawley rats were given either 1 or 32 days of voluntary access respectively to 7% (v/v) ethanol solution before being injected once with 30 mg/kg of morphine. Alcohol consumption during the subsequent week was suppressed to about the same extent in both cases. Food intake was slightly reduced and water drinking increased in both groups after the morphine injection. The only difference observed between the effects after 1 and 32 days of alcohol access was that in the latter there was a significant negative correlation (r = −.891) between the reductions in alcohol and food consumption. The results suggest that the suppression of alcohol drinking is not dependent upon those factors, such as the ability to show an alcohol-deprivation effect, which develop during prolonged access to alcohol.

J.D. Sinclair

Papers

Morphine suppresses alcohol drinking regardless of prior alcohol access duration