Biomaterial Database

Action of ethanol on responses to nicotine from cerebellar interneurons and medial septal neurons: relationship to methyllycaconitine inhibition of nicotine responses. 1999

X Yang, and H E Criswell, and G R Breese

Department of Psychiatry and Anesthesiology, North Carolina Neurosciences Center, School of Medicine, University of North Carolina at Chapel Hill, 27599-7178, USA.

BACKGROUND A majority of alcoholics also smoke, suggesting that alcohol and nicotine share a common action on nicotinic cholinergic receptors. METHODS Extracellular single-unit recording was used to investigate the effects of ethanol on responses to nicotine from rat cerebellar interneurons and medial septal neurons. RESULTS Nicotine produced inhibition from medial septal neurons, but increased neural activity of cerebellar interneurons. When ethanol was applied locally to cerebellar interneurons, the excitatory response to nicotine was enhanced in a dose-related manner. Nicotine-induced inhibition from medial septal neurons was reduced by ethanol from the majority of neurons, but a dose relationship for this inhibition by ethanol was not observed. Ethanol affected responses to nicotine from over 90% of all neurons investigated at these sites. Initially, it was established that the nicotinic antagonists, methyllycaconitine (MLA) and alpha-bungarotoxin, which affect a nicotinic cholinergic (nACh) receptor with an alpha7 subunit, had similar actions on responses to nicotine from individual medial septal cells and cerebellar interneurons. When MLA was tested against responses to nicotine from neurons in the two brain regions, MLA antagonized responses to nicotine from only 27% of the neurons rather than the 90% found for ethanol. This latter observation provided evidence that ethanol was affecting neurons with MLA-insensitive receptors. When the actions of ethanol on responses to nicotine were compared directly with the action of MLA on the same medial septal neurons, both ethanol and MLA caused a greater than 50% antagonism of the response to nicotine, indicative that nACh receptors with the alpha7 subunit were sensitive to ethanol. CONCLUSIONS Collectively, these data provide evidence that ethanol affects responses to nicotine not only from nACh receptors on medial septal cells and cerebellar interneurons containing an alpha7 subunit (i.e., MLA-sensitive receptors), but also from nACh receptor subtypes without this specific nACh receptor subunit (i.e., MLA-insensitive receptors).

UI	MeSH Term	Description	Entries
D007395	Interneurons	Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.	Intercalated Neurons,Intercalated Neuron,Interneuron,Neuron, Intercalated,Neurons, Intercalated
D008297	Male		Males
D009538	Nicotine	Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.	Nicotine Bitartrate,Nicotine Tartrate
D011978	Receptors, Nicotinic	One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.	Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D002492	Central Nervous System Depressants	A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents).	CNS Depressants,Depressants, CNS
D002531	Cerebellum	The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.	Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D000157	Aconitine	A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM; DELPHINIUM and larkspurs. It activates VOLTAGE-GATED SODIUM CHANNELS. It has been used to induce ARRHYTHMIAS in experimental animals and it has anti-inflammatory and anti-neuralgic properties.	Acetylbenzoylaconine,Aconitane-3,8,13,14,15-pentol, 20-ethyl-1,6,16-trimethoxy-4-(methoxymethyl)-, 8-acetate 14-benzoate, (1alpha,3alpha,6alpha,14alpha,15alpha,16beta)-,Acetylbenzoyl-aconine,Acetylbenzoyl aconine
D000431	Ethanol	A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.	Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012686	Septal Nuclei	Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of FOREBRAIN and BRAIN STEM areas including the HIPPOCAMPAL FORMATION, the LATERAL HYPOTHALAMUS, the tegmentum, and the AMYGDALA. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis.	Bed Nucleus of Stria Terminalis,Nucleus of Anterior Commissure,Nucleus of Diagonal Band,Nucleus of Stria Terminalis,Septofimbrial Nucleus,Dorsal Septal Nucleus,Lateral Septal Nucleus,Lateral Septum Nucleus,Medial Septal Nucleus,Medial Septum Nucleus,Nucleus Interstitialis Striae Terminalis,Nucleus Lateralis Septi,Nucleus Septalis Lateralis,Nucleus Septi Lateralis,Nucleus Striae Terminalis,Nucleus Triangularis Septi,Nucleus of the Stria Terminalis,Septal Nuclear Complex,Triangular Septal Nucleus,Anterior Commissure Nucleus,Complex, Septal Nuclear,Complices, Septal Nuclear,Diagonal Band Nucleus,Laterali, Nucleus Septalis,Laterali, Nucleus Septi,Lateralis Septi, Nucleus,Lateralis Septus, Nucleus,Lateralis, Nucleus Septalis,Lateralis, Nucleus Septi,Nuclear Complex, Septal,Nuclear Complices, Septal,Nuclei, Septal,Nucleus Lateralis Septus,Nucleus Septalis Laterali,Nucleus Septi Laterali,Nucleus Striae Terminali,Nucleus Triangularis Septus,Nucleus, Dorsal Septal,Nucleus, Lateral Septal,Nucleus, Lateral Septum,Nucleus, Medial Septal,Nucleus, Medial Septum,Nucleus, Septofimbrial,Nucleus, Triangular Septal,Septal Nuclear Complices,Septal Nucleus, Dorsal,Septal Nucleus, Lateral,Septal Nucleus, Medial,Septal Nucleus, Triangular,Septalis Laterali, Nucleus,Septalis Lateralis, Nucleus,Septi Laterali, Nucleus,Septi Lateralis, Nucleus,Septi, Nucleus Lateralis,Septi, Nucleus Triangularis,Septum Nucleus, Lateral,Septum Nucleus, Medial,Septus, Nucleus Lateralis,Septus, Nucleus Triangularis,Stria Terminalis Nucleus,Striae Terminali, Nucleus,Striae Terminalis, Nucleus,Terminali, Nucleus Striae,Terminalis, Nucleus Striae,Triangularis Septi, Nucleus,Triangularis Septus, Nucleus