S.S. Chirwa

Intraarticular bupivacaine (Marcaine) after arthroscopic meniscectomy: a randomized double-blind controlled study.

In this study, 79 patients undergoing arthroscopic meniscectomy were entered into a randomized double-blind controlled trial in which intraarticular bupivacaine (Marcaine), was compared with a saline placebo. Intraarticular bupivacaine was shown to be an effective and safe method of achieving analgesia after arthroscopic meniscectomy.

Functional Expression of Brain Neuronal CB2 Cannabinoid Receptors Are Involved in the Effects of Drugs of Abuse and in Depression

Major depression and addiction are mental health problems associated with stressful events in life with high relapse and recurrence even after treatment. Many laboratories were not able to detect the presence of CB2 cannabinoid receptors (CB2‐Rs) in healthy brains, but CB2‐R expression has been demonstrated in rat microglial cells and other brain‐associated cells during inflammation. Thus, neuronal expression of CB2‐Rs has been ambiguous and controversial, and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of the CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances, including opiates, cocaine, and ethanol, in rodents. Here we demonstrate that a high incidence of Q63R but not H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2‐Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated after exposure to stressors and administration of abused drugs. Mice that developed an alcohol preference had reduced CB2 gene expression, and chronic treatment with JWH015 a putative CB2‐R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 antisense oligonucleotide into the mouse brain reduced mouse aversions in the plus‐maze test, indicating the functional presence of CB2‐Rs in the brain that modifies behavior. Using electron microscopy we report the subcellular localization of CB2‐Rs that are mainly on postsynaptic elements in rodent brain. Our data demonstrate the functional expression of CB2‐Rs in the brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuroimmunocannabinoid activity.

Age-dependent changes in cat masseter nerve: an electrophysiological and morphological study

The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study.

Substances released during tetanic stimulation of rabbit neocortex induce neurite growth in PC-12 cells and long-term potentiation in guinea pig hippocampus

Samples collected from rabbit neocortical surface during a tetanic stimulation of the neocortex induced neurite growth in PC-12 cells in culture and synaptic long-term potentiation (LTP) in guinea pig hippocampal slices. If these samples were preheated and cooled, or if they were collected in the absence of a tetanic stimulation of the rabbit neocrotex, they did not induce neurite growth in PC-12 cells or LTP in the guinea pig hippocampus. These results suggest that neurite-inducing factors are released during tetanic stimulations and that these substances are involved in LTP.

Ibogaine Signals Addiction Genes and Methamphetamine Alteration of Long‐Term Potentiation

Abstract: The mapping of the human genetic code will enable us to identify potential gene products involved in human addictions and diseases that have hereditary components. Thus, large‐scale, parallel gene‐expression studies, made possible by advances in microarray technologies, have shown insights into the connection between specific genes, or sets of genes, and human diseases. The compulsive use of addictive substances despite adverse consequences continues to affect society, and the science underlying these addictions in general is intensively studied. Pharmacological treatment of drug and alcohol addiction has largely been disappointing, and new therapeutic targets and hypotheses are needed. As the usefulness of the pharmacotherapy of addiction has been limited, an emerging potential, yet controversial, therapeutic agent is the natural alkaloid ibogaine. We have continued to investigate programs of gene expression and the putative signaling molecules used by psychostimulants such as amphetamine in in vivo and in vitro models. Our work and that of others reveal that complex but defined signal transduction pathways are associated with psychostimulant administration and that there is broad‐spectrum regulation of these signals by ibogaine. We report that the actions of methamphetamine were similar to those of cocaine, including the propensity to alter long‐term potentiation (LTP) in the hippocampus of the rat brain. This action suggests that there may be a “threshold” beyond which the excessive brain stimulation that probably occurs with compulsive psychostimulant use results in the occlusion of LTP. The influence of ibogaine on immediate early genes (IEGs) and other candidate genes possibly regulated by psychostimulants and other abused substances requires further evaluation in compulsive use, reward, relapse, tolerance, craving and withdrawal reactions. It is therefore tempting to suggest that ibogaine signals addiction gene products.

STRYCHNINE ANTAGONIZES JAW-CLOSER MOTONEURON IPSPS INDUCED BY RETICULAR STIMULATION DURING ACTIVE SLEEP

In chronic, unanesthetized, normally respiring cats, stimulation of the nucleus reticularis pontis oralis induced inhibitory postsynaptic potentials (IPSPs) in masseter motoneurons during active sleep, but not during wakefulness or quiet sleep. Strychnine, when applied juxtacellularly by microiontophoresis to masseter motoneurons, specifically suppressed the active sleep-dependent IPSPs. In contrast, bicuculline did not suppress the active sleep-dependent IPSPs. These results indicate these IPSPs are mediated by the putative neurotransmitter glycine.

Are Nerve Growth Factors Involved in Long-Term Synaptic Potentiation in the Hippocampus and Spatial Memory?

Nerve growth factor (NGF), which facilitates the development of the nervous system (levi-Montalcini and Angeletti, 1968), is present in the hippocampus and is known to be released following injury to hippocampal pathways (Crutcher and Collins, 1986; Nieto-Sampedro and Cotman, 1985). NGF is believed to be released from the postsynaptic neurons and taken up by the presynaptic terminals; it causes sprouting of boutons and brings about biochemical changes in the presynaptic terminals (Hendry et al., 1974; Springer and Loy, 1985). High frequency activation of hippocampal afferents causes a subsequent long-term potentiation (LTP) of synaptic transmission (Bliss and Lomo, 1973) between these inputs and the pyramidal neurons. The mechanisms involved in the induction and maintenance of this potentiation are of significant interest to neuroscientists because of its presumed involvement in learning and memory, two of the most important functions of the brain. A depolarization of the CA1 neurons in association with presynaptic activity and a patterned stimulation of hippocampal inputs in association with theta rhythm are both thought to be necessary for LTP (Kelso et al., 1986; Larson and Lynch, 1986; Sastry et al., 1986; Wigstrom et al., 1986). How a cooperation between the activity in the presynaptic terminal and a depolarization of the postsynaptic neuron can lead to LTP is not clear. As one of the possibilities, we previously suggested that the postsynaptic depolarization induces the release of a chemical which acts on the stimulated presynaptic terminal to cause further.

An in vivo model for investigating bilateral synaptic plasticity across CA3/CA1 synapses in guinea pig dorsal hippocampus

A method is described for concurrent investigation of long-term potentiation (LTP) in the left and right CA1 synapses in dorsal hippocampi in guinea pig in vivo. Briefly, animals are anesthetized with urethane, and small access holes are made in the skull through which electrodes are lowered to stimulate the left CA3 and record from both CA1 regions. Using this animal model, we have found that LTP is produced in both CA1 regions, following conditioning stimulation to the left CA3. However, in some animals LTP occurred in the left CA1 without concomitant synaptic potentiation in the contralateral CA1. We also observed that in some experiments synaptic potentiation in the contralateral CA1, when present, decayed to baseline levels even though LTP persisted in the ipsilateral CA1. To conclude, our data on bilateral LTP demonstrates findings that are best addressed in vivo.

Asynchronous synaptic responses in hippocampal CA1 neurons during synaptic long-term potentiation

In guinea pig hippocampal slices incubated in Ba2+, stimulation of stratum radiatum induced an EPSP that was followed by an increased frequency of miniature EPSPs in CA1 neurons. These miniature EPSPS, which were presumably due to the asynchronous release of transmitter, were increased after the induction of long-term potentiation.

Blockade of hippocampal long-term potentiation by saccharin

Population spikes, population excitatory postsynaptic potentials and intracellular excitatory postsynaptic potentials were recorded in the CA1 area of guinea-pig hippocampal slices in response to low frequency stimulation of the stratum radiatum. Tetanic stimulation of the same afferents during an application of saccharin (10 mM, 10 min) failed to induced a long-term potentiation of the population spike, population excitatory postsynaptic potential and intracellularly recorded excitatory postsynaptic potential. A post-tetanic application of saccharin did not prevent long-term potentiation of the population spike from developing. Saccharin did not change the input resistance, the membrane potential or the ability to induce action potentials in the CA1 neurons. The slope of the intracellular excitatory postsynaptic potentials recorded in normal medium, in normal medium containing 2-amino-5-phosphonovalerate, or in Mg(2+)-free medium containing 6-cyano-7-nitroquinoxaline-2,3-dione was not significantly altered by saccharin. The depolarizations of CAI neurons produced by superfusion of N-methyl-D-aspartate or during a brief tetanic stimulation of the stratum radiation were also not altered by the drug. It therefore appears that saccharin blocks the induction of long-term potentiation by a mechanism that does not involve a blockade of N-methyl-D-aspartate receptors. Application of fluid samples collected from rabbit neocortical surface during a tetanic stimulation of the neocortex caused neurite growth in PC-12 cells, suggesting that growth-related substances were present in the collected samples. If these samples were superfused onto hippocampal slices, long-term potentiation developed. If however, the samples were co-applied with saccharin, neither neurite growth in PC-12 cells nor long-term potentiation in hippocampal slices was observed, raising the possibility that growth-related substances are involved in long-term potentiation.