PubMed · 577987
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G G Harrison. 1977-08-29. Cardiac arrest.. https://doi.org/10.1001/jama.1977.03280100022011
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Trauma and injury necessitate the use of various surgical interventions, yet such procedures themselves are invasive and often interrupt synaptic communications in the nervous system. Because anesthesia is required during surgery, it is important to determine whether long-term exposure of injured nervous tissue to anesthetics is detrimental to regeneration of neuronal processes and synaptic connections. In this study, using identified molluscan neurons, we provide direct evidence that the anesthetic propofol blocks cholinergic synaptic transmission between soma-soma paired Lymnaea neurons in a dose-dependent and reversible manner. These effects do not involve presynaptic secretory machinery, but rather postsynaptic acetylcholine receptors were affected by the anesthetic. Moreover, we discovered that long-term (18-24 h) anesthetic treatment of soma-soma paired neurons blocked synaptogenesis between these cells. However, after several hours of anesthetic washout, synapses developed between the neurons in a manner similar to that seen in vivo. Long-term anesthetic treatment of the identified neurons visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1) and the electrically coupled Pedal A cluster neurons (PeA) did not affect nerve regeneration in cell culture as the neurons continued to exhibit extensive neurite outgrowth. However, these sprouted neurons failed to develop chemical (VD4 and LPeD1) and electrical (PeA) synapses as observed in their control counterparts. After drug washout, appropriate synapses did reform between the cells, although this synaptogenesis required several days. Taken together, this study provides the first direct evidence that the clinically used anesthetic propofol does not affect nerve regeneration. However, the formation of both chemical and electrical synapses is severely compromised in the presence of this drug. This study emphasizes the importance of short-term anesthetic treatment, which may be critical for the restoration of synaptic connections between injured neurons.
Evaluations of new emission tomography ligands are usually carried out in animals. In order to keep the animals in a restricted position during the scan session, anaesthesia is almost inevitable. In ex vivo rat studies we investigated the interference of ketamine/xylazine, zoletile mixture, isoflurane and halothane with the serotonin re-uptake site, the serotonin(2A) receptor and the dopamine re-uptake site by use of [(3)H]-(S)-citalopram, [(18)F]altanserin and [(125)I]PE2I, respectively. Ketamine/xylazine decreased the target-to-background ratio (mean +/- SD) of [(3)H]-( S)-citalopram from 1.5+/-0.19 to 0.81+/-0.19 (P<0.05), whereas isoflurane and halothane increased the ratio from 1.5+/-0.19 to 1.9+/-0.24 and 2.1+/-0.13 (P<0.05), respectively. Only with the zoletile mixture did the ratio remain unaltered. None of the tested anaesthetics affected the target-to-background ratio of [(18)F]altanserin. The [(125)I]PE2I target-to-background ratio decreased with both ketamine/xylazine (from 12.4+/-0.81 to 10.1+/-1.4, P<0.05) and isoflurane (from 12.4+/-0.81 to 9.5+/-1.1, P<0.05) treated rats, whereas treatment with zoletile mixture and halothane left the ratio unaltered. It is concluded that prior to performance of neuroreceptor radioligand studies, the possible interaction between radioligands and anaesthetics should be carefully evaluated.
The delta subunit of the gamma-aminobutyric acid (A) receptor (GABA(A)R) is expressed postnatally mostly in the cerebellum, thalamus, and dentate gyrus. Previous studies in mice with a targeted disruption of the delta subunit revealed a considerable attenuation of behavioral responses to neuroactive steroids but not to other neuromodulatory drugs. Here we show that delta subunit loss leads to a concomitant reduction in hippocampal alpha4 subunit levels. These changes were accompanied by faster decay of evoked inhibitory postsynaptic potentials (IPSPs) in dentate granule neurons of -/- mutants (decay tau = 25 ms) compared with +/+ controls (tau = 50 ms). Furthermore, the GABA(A)R-mediated miniature inhibitory postsynaptic currents (mIPSCs) also decayed faster in delta-mutants (tau = 6.3 ms) than controls (tau = 7.2 ms) and had decreased frequency (controls, 10.5 Hz; mutants, 6.6 Hz). Prolongation of mIPSCs by the neuroactive steroid anesthetic, alphaxalone (1-10 microM), was smaller in delta-mutants (at 10 microM, 65% increase) compared with +/+ littermates (308% increase). In competition binding experiments, alphaxalone (0.03-1 microM) modulation of [35S]t-butylbicyclophosphorothionate binding was reduced in delta-mutant brain homogenates, indicating that the decreased alphaxalone effects on mIPSCs were due to changes in the GABA(A)R protein. Faster decay of evoked IPSPs and mIPSCs in delta-mutants suggests presence of the delta subunit at both synaptic and extrasynaptic GABA(A)Rs. Decreased synaptic and extrasynaptic inhibition likely contributes to the pro-epileptic phenotype of delta-mutants. Reduced neurosteroid sensitivity might also contribute to seizure susceptibility. While the simplest explanation is that delta subunit-containing GABA(A)Rs represent the actual target of neurosteroids, it is possible that the behavioral and physiological sensitivity to neuroactive steroids is indirectly altered in the delta -/- mice.