Dopamine, serotonin, cholinergic and somatostatin responses to aging have been followed in striatum and hippocampus of two inbred strains of mice (C57BL and BALB/c). A striking strain dependency is noted. Dopaminergic mechanisms in BALB/c mice become particularly defective in striatum where both dopamine release and dopamine turnover are affected. Also, striatal cholinergic activity and somatostatin levels are more disturbed in BALB/c than in C57BL mice. For cholinergic neurotransmission and somatostatin levels, similar results are noted in hippocampus. Conversely, C57BL mice react to aging by increased serotonin turnover in hippocampus and decreased 5HIAA levels in both structures studied, whereas the BALB/c strain remains unaffected. Also, structure dependency is observed: in C57BL mice serotonin turnover appears to be unchanged in striatum and increased in hippocampus; in the BALB/c the slowing down of dopamine activity in striatum is not observed in hippocampus. This unequal capacity of central neurotransmitters and neuromodulators to adapt to aging processes, depending upon the genotype, the nervous structure and the neurotransmitter considered may be involved in man in specific pathologies in aged individuals.

Acetylcholine↗

PubMedDate not supplied

Influence of mouse genotype on responses of central cholinergic neurotransmission to long term alcohol intoxication.

Cholinergic neurotransmission has been followed in striatum and hippocampus in two inbred strains of mice (C57Bl/6 and Balb/c) during long term alcohol exposure (over a 25 month period) and with aging. Marked strain dependent differences in reactivity of pre- and postsynaptic cholinergic markers to chronic alcohol exposure and aging were demonstrated in both structures. The Balb/c strain exhibits a remarkable long lasting tolerance to alcohol injury for striatal and hippocampal cholinergic markers (choline acetyltransferase, high affinity choline uptake, muscarinic receptors affinity, acetyl cholinesterase), whereas C57Bl mice appear more sensitive to alcohol intoxication. Likewise aging affects the C57Bl mouse more severely than the Balb/c, a phenomenon which may be involved in the sensitivity of these mice to alcohol intoxication. Moreover long term alcohol exposure, in addition to aging show unequal effects on the diverse cholinergic markers studied. Also divergences of specific brain areas have been noted and should be related to their particular neuroanatomy. Such discrepancies may, in part, explain differences observed in the behavioral effects of chronic alcohol intoxication in alcoholics.

Acetylcholinesterase↗

PubMedDate not supplied

Influence of mouse genotype on responses of central biogenic amines to alcohol intoxication and aging.

Dopamine and serotonin responses to various periods of alcohol treatment have been followed in striatum and hippocampus of two inbred strains of mice and related to the effect of aging. A striking strain dependency was noted for chronic alcohol effects and also for senescence. For both neurotransmitters studied the C57Bl strain loses tolerance to prolonged alcohol injury earlier than the Balb/c strain. This loss of tolerance accompanying aging may be indicative of more widespread changes in CNS adaptability in this strain. The unequal capacity to adapt also appears to depend on the nervous structure and the neurotransmitter considered. Alcohol and aging induced changes are not identical. In a given mouse strain, significant effects of either drug or aging induced disturbances are noted. A similar molecular process could operate in both aging and alcohol abuse, but the neurochemical effect might depend on the nervous structure or neurotransmitter involved. Such a phenomenon may be the basis of differences in behavioral changes observed in alcoholics.

Aging↗

PubMedDate not supplied

Genotypic variations in ethanol effect on striatal and hippocampal transmitter interactions.

Genotypic variations in the reactivity to an acute ethanol intoxication of dopamine turnover, release and metabolites, as well as serotoninergic neurotransmission have been investigated in the nigrostriatal and the septohippocampal pathways of C57Bl and Balb/c mice strains. In the striatum, decreased dopamine release associated with increased DA turnover, was noted after alcohol treatment, possibly as a retrocontrol reaction. Parallely, enhanced serotonin metabolism occurred. For the septohippocampal pathway, dopamine neurotransmission in the septum reacts to alcohol in a similar way as in the striatum. In the hippocampus, serotonin metabolism is reduced. A strain dependent difference in sensitivity to ethanol is observed for both pathways. The results are discussed (1) in the context of interactions of these transmitters with cholinergic activity; (2) in relation with behavioral disturbances associated to alcohol abuse in man (motor incoordination and memory alterations, in particular).

Alcoholic Intoxication↗

PubMedDate not supplied