The effects of ethanol on gamma-aminobutyric acid-induced depressions of cerebellar Purkinje neurons: influence of beta adrenergic receptor action in young and aged Fischer 344 rats.
We reported previously that both the systemic administration and the local application of ethanol potentiated gamma-aminobutyric acid (GABA)-induced depressions of cerebellar Purkinje neurons if the GABA responses were concomitantly facilitated (positively modulated) by a beta adrenergic agonist, such as isoproterenol (ISO). In the present study we investigated the influence of aging on the beta adrenergic sensitization of GABA responses in young and aged Fischer 344 (F344) rats which exhibit age-related deficits in beta adrenergic receptor functions in the cerebellum. We found that the efficacy of ISO to modulate GABA responses was less in aged F344 rats vs. young F344 rats and that ethanol potentiated further the ISO-facilitated GABA responses of only 15% of the cerebellar Purkinje neurons recorded from aged F344 rats compared to 56% of the neurons from young F344 rats. Furthermore, in aged F344 rats, local applications of ISO frequently attenuated (negatively modulated) GABA responses of cerebellar Purkinje neurons and ethanol decreased further these attenuated GABA responses. Similar interactions were only observed infrequently from young F344 rats. In addition, these data suggest that age-related changes in the function of beta adrenergic mechanisms in the cerebellum are reflected not only in the decreased frequency of neurons exhibiting ethanol potentiation of ISO-modulated GABA effects but also in the observation that ethanol reduced GABA responses even in the presence of beta adrenergic receptor stimulations. This latter ethanol effect may also involve a beta adrenergic mechanism.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
A M
AM
Lin
P C
PC
Bickford
M R
MR
Palmer
D000375:Aging / Q000502:physiology*; D000818:Animals; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013999:Timolol / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D013999:Timolol; D007545:Isoproterenol