Alterations of neocortical neuronal responses to acetylcholine and GABA in rats born to alcohol-dependent mothers.
Alcohol is known to be a CNS teratogenic factor interfering with neuronal and synaptic maturation. The purpose of this microiontophoretic study was to explore GABAergic and cholinergic central mechanisms in adult rats exposed to alcohol in the third phase of prenatal life (ADM), when their mothers were subjected to alcohol physical dependence induction (9.6 g/kg/day). Responses to acetylcholine and GABA were recorded in frontal and somatosensory cortical neurons. Adult rats, whose mothers had been administered placebo with identical procedures, were used as a control (C). Cholinergic responses were significantly decreased and GABAergic responses increased in ADM animals with respect to controls. After a single i.p. alcohol injection (1.6 g/kg) spontaneous firing was depressed in ADM animals to a lesser extent than in C rats. Cholinergic excitations were reduced in C group and potentiated with reversal of atropine antagonism in ADM animals. GABAergic inhibitions were slightly increased and bicuculline antagonism was blocked in C rats, while ADM animals showed decreased responses to GABA. The present results support the hyperactivity of GABAergic system and the hypoactivity of cholinergic system reported in previous studies on prenatally and postnatally alcohol-exposed animals. Microiontophoretic results following ethanol injection led to the hypothesis that a rapid tolerance/dependence may develop in the offspring of alcohol-dependent rats.
Janiri
L
L
Department of Psychiatry, Faculty of Medicine, Catholic University, Rome, Italy.
Gobbi
G
G
Persico
A M
AM
Santarelli
M
M
Minciacchi
D
D
Tempesta
E
E
D000109:Acetylcholine / Q000494:pharmacology*; D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D007478:Iontophoresis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009460:Neurologic Examination / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005680:gamma-Aminobutyric Acid; D001285:Atropine; D000109:Acetylcholine; D001640:Bicuculline