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The review article by Nevo and Hamon examines selectively and evaluates many of the recent research findings on the possible role of neurotransmitters in the development of alcohol abuse and alcoholism. Intriguing evidence now exists that certain monoaminergic and amino acid neurotransmitters as well as other factors are involved neurochemically in the actions of alcohol. Our critique introduces alternative viewpoints to several of the notions held today about alcohol's effect on neurotransmitter systems in the brain. Caveats are also raised in terms of the interpretation of observations, particularly in relation to procedures used for determining the effects of alcohol on these systems. The reason for the need to consider these alternative views and interpretations centers on the fact that what may appear on the surface to be straightforward may actually represent an oversimplification of the true complexity of the addictive liability to alcohol or those biological components underpinning the disease of alcoholism.

M c Millen, B. A., L. W. Means, J. Matthews. Comparison of the alcohol-preferring P rat to the Wistar rat in behavioral tests of impulsivity and anxiety. PHYSIOL BEHAV 63(3) 371–375, 1998.—To determine whether the selectively bred alcohol preferring P rat displays impulsive and anxiety-related behaviors, as have been noted in Type 2 human alcoholics, P rats were compared with outbred Wistar rats, the strain from which P rats were derived, on a series of behaviors reflecting impulsivity and anxiety. The two groups were also compared on their volitional consumption of ethanol. When compared with the Wistar rats, the P rats preferred a higher concentration of ethanol and imbibed a much greater amount of ethanol when they were offered their preferred concentration. However, the behavioral tasks produced inconsistent results. The P rats completed 100 bar presses for food in less time when tested on a constant reinforcement schedule, which suggests that they are hyperactive compared to Wistar rats. However, the P rats also emitted a higher percentage of reinforced responses on differential reinforcement of low rate responding (DRL)-10s and gnawed less from a cork stopper, which suggests that they are less impulsive and possibly neophobic. The two groups did not differ on emergence into or activity in an open field, their activity in or open-arm duration in the elevated plus maze, or performance on DRL-5s and DRL-15s. Collectively, the behavioral data suggest that P rat does not serve as a model for the anxiety and impulsiveness associated with the Type 2 alcoholic individual.

The hypothesis that the nerve endings of the dopamine projection of the frontal cortex lack autoreceptors for regulation of tyrosine hydroxylase was tested by using the preferential inhibitors of dopamine autoreceptors, molindole and buspirone. In contrast to haloperidol, which elevates dopamine metabolism in the striatum and frontal cortex, both molindone and buspirone elicited little change in dopamine metabolism in the frontal cortex at doses up to 3.0 mg/kg, which cause the same maximal response in the corpus striatum as does haloperidol. Thus, the lack of autoreceptors in the frontal cortex is of pharmacological importance. That preferential inhibition of striatal dopamine autoreceptors may reverse catalepsy by enhancing synthesis and release of dopamine was tested by first inducing catalepsy with different drugs and then administering molindone or buspirone. Only buspirone (1.0 mg/kg) reversed catalepsy. This effect does not require presynaptic dopamine as catalepsy was reversed by buspirone in the dopamine-depleted rat (with 2.0 mg/kg R04-1284) as well as after postsynaptic dopamine receptor blockade by haloperidol of cis-flupenthixol. Thus, the mechanism for the reversal of catalepsy appears to be located efferent from the dopamine neuron. Buspirone, a non-benzodiazepine anti-anxiety drug, may prove useful for treatment of extrapyramidal motor disorders of either iatrogenic or idiosyncratic origin.