scholarly journals Prolonged morphine exposure during adolescence alters the responses of lateral paragigantocellularis neurons to naloxone in adult morphine dependent rats

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Sara Sabuee ◽  
S. Mohammad Ahmadi-Soleimani ◽  
Hossein Azizi
Keyword(s):  
Adolescent Male ◽  
Neuronal Responses ◽  
Cellular Mechanisms ◽  
Unit Recording ◽  
Free Interval ◽  
Baseline Activity ◽  
Opioid Drugs ◽  
Male Wistar Rats ◽  
Excitatory Responses ◽  
Drug Free

Abstract Introduction Adolescence is a critical period in brain development, and it is characterized by persistent maturational alterations in the function of central nervous system. In this respect, many studies show the non-medical use of opioid drugs by adolescents. Although this issue has rather widely been addressed during the last decade, cellular mechanisms through which adolescent opioid exposure may induce long-lasting effects are not duly understood. The present study examined the effect of adolescent morphine exposure on neuronal responses of lateral paragigantocellularis nucleus to naloxone in adult morphine-dependent rats. Methods Adolescent male Wistar rats (31 days old) received increasing doses of morphine (from 2.5 to 25 mg/kg, twice daily, s.c.) for 10 days. Control subjects were injected saline with the same protocol. After a drug-free interval (20 days), animals were rendered dependent on morphine during 10 days (10 mg/kg, s.c., twice daily). Then, extracellular single-unit recording was performed to investigate neural response of LPGi to naloxone in adult morphine-dependent rats. Results Results indicated that adolescent morphine treatment increases the number of excitatory responses to naloxone, enhances the baseline activity and alters the pattern of firing in neurons with excitatory responses in adult morphine-dependent rats. Moreover, the intensity of excitatory responses is reduced following the early life drug intake. Conclusion It seems that prolonged opioid exposure during adolescence induces long-lasting neurobiological changes in LPGi responsiveness to future opioid withdrawal challenges.

A Code for Spatial Alternation During Fixation in Rat Hippocampal CA1 Neurons

2009 ◽  
Vol 102 (1) ◽  
pp. 556-567 ◽  
Author(s):  
Muneyoshi Takahashi ◽  
Johan Lauwereyns ◽  
Yoshio Sakurai ◽  
Minoru Tsukada
Keyword(s):  
Internal Representation ◽  
Spatial Choice ◽  
Unit Recording ◽  
Ca1 Neurons ◽  
Spatial Alternation ◽  
Baseline Activity ◽  
Hippocampal Ca1 ◽  
Male Wistar Rats ◽  
The Right ◽  
Alternation Task

The classical notion of hippocampal CA1 “place cells,” whose activity tracks physical locations, has undergone substantial revision in recent years. Here, we provide further evidence of an abstract spatial code in hippocampal CA1, which relies on memory and adds complexity to the basic “place cell.” Using a nose-poking paradigm with four male Wistar rats, we specifically concentrated on activity during fixation, when the rat was immobile and waiting for the next task event in a memory-guided spatial alternation task. The rat had to alternate between choosing the right and left holes on a trial-by-trial basis, without any sensory cue, and relying on an internal representation of the sequence of trials. Twelve tetrodes were chronically implanted for single-unit recording in the right CA1 of each rat. We focus on 76 single neurons that showed significant activation during the fixation period compared with baseline activity between trials. Among these 76 fixation neurons, we observed 38 neurons that systematically changed their fixation activity as a function of the alternation sequence. That is, even though these rats were immobile during the fixation period, the neurons fired differently for trials in which the next spatial choice should be left (i.e., RIGHT-TO-LEFT trials) compared with trials in which the next spatial choice should be right (i.e., LEFT-TO-RIGHT trials), or vice versa. Our results imply that these neurons maintain a sequential code of the required spatial response during the alternation task and thus provide abstract information, derived from memory, that can be used for efficient navigation.

Spinal NMDA Receptors Contribute to Neuronal Processing of Acute Noxious and Nonnoxious Colorectal Stimulation in the Rat

2001 ◽  
Vol 86 (4) ◽  
pp. 1783-1791 ◽  
Author(s):  
Yaping Ji ◽  
Richard J. Traub
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Nmda Receptor Antagonist ◽  
Evoked Responses ◽  
Neuronal Responses ◽  
Unit Recording ◽  
Mk 801 ◽  
Colorectal Distention ◽  
Evoked Activity ◽  
Excitatory Responses

The present study investigated the role of NMDA receptors in the spinal processing of acute noxious and nonnoxious colorectal stimulation using extracellular single-unit recording in the rat. Fifty-three neurons in the L6–S2 dorsal horn of the spinal cord were studied. Neurons were identified using touch and light pinch of the ipsilateral perianal/scrotal area and colorectal distention (CRD). All neurons had excitatory responses to CRD. Thirty neurons were studied using a search stimulus of 80-mmHg CRD. The effects of a systemically administered N-methyl-d-aspartate (NMDA) receptor channel blocker, dizocilpine maleate (MK-801) (0.1, 0.5, 1.0, and 5.0 mg/kg), were tested on the CRD-evoked responses of 13 neurons. The lowest dose had no effect on the neuronal responses to CRD, while greater doses lowered the CRD-evoked responses at all distention pressures tested (20, 40, 60, and 80 mmHg). Similarly, spinal application of MK-801 (20, 50, 100, and 200 nmol) attenuated CRD-evoked activity ( n = 9). In addition, a spinally administered competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (30, 60, 120, and 240 nmol), dose-dependently attenuated the CRD-evoked response at all distention pressures ( n = 5). Systemically administered APV did not affect neuronal responses to CRD ( n = 3). Twenty-three neurons were studied in animals that never received distention pressures exceeding 30 mmHg; the search stimulus ranged between 20- and 30-mmHg CRD. These neurons were tested using 20-mmHg CRD. Systemically administered MK-801 facilitated the response to 20-mmHg CRD in three neurons and inhibited the response in five neurons, and the response of five neurons was not affected. Spinally administered MK-801 had no effect on neuronal responses to 20-mmHg CRD in six neurons. However, spinally administered APV dose-dependently decreased the response to 20-mmHg CRD in four neurons. These results are consistent with our previous observations that used Fos expression as the index, suggesting that spinal NMDA receptors contribute to processing of both noxious and nonnoxious CRD.

scholarly journals Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3811-3817 ◽  
Author(s):  
Ashish Jain ◽  
Joseph A. Kovacs ◽  
David L. Nelson ◽  
Stephen A. Migueles ◽  
Stefania Pittaluga ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Intracellular Cytokine Staining ◽  
Cd40 Ligand ◽  
Genetic Alterations ◽  
Delayed Type Hypersensitivity ◽  
Free Interval ◽  
Hyper Igm Syndrome ◽  
Hyper Igm ◽  
Drug Free

Abstract X-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.03 mg/kg for 22 weeks, and after a 12-week drug-free interval, the dose was increased to 0.05 mg/kg for an additional 22 weeks of treatment. Although specific antibody responses to T cell–dependent antigens was lacking, administration of rCD40 resulted in acquisition of the capacity to mount cutaneous delayed type hypersensitivity reactions that disappeared during the drug-free interval as well as the postbiologic follow-up period. With rCD40L treatment, patient T cells developed a new capacity to respond to T-cell mitogens with synthesis of IFN-γ and TNF-α. Intracellular cytokine staining studies showed that both CD4+ and CD8+ T cells participated in this response. Finally, CD40L therapy was associated with changes in lymph node size and architecture based on comparison of biopsies taken before and after therapy. This clinical study showed that rCD40L is capable of improving T cell–immune function in patients with XHM.

scholarly journals Neurobiology of opioid dependence in creating addiction vulnerability

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1748 ◽  
Author(s):  
Christopher J. Evans ◽  
Catherine M. Cahill
Keyword(s):  
Stressful Life Event ◽  
Physical Symptoms ◽  
Addictive Behaviors ◽  
Cellular Mechanisms ◽  
Opioid Drugs ◽  
The Usa ◽  
Drug Dependent ◽  
Neuronal Systems ◽  
Long Acting ◽  
Dependent State

Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality — the “drug-dependent” state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadone or buprenorphine, is generally indistinguishable from the drug-naïve state for most overt behaviors. The consequences of the allostatic changes (cellular, circuit, and system adaptations) that accompany the drug-dependent state are revealed during drug withdrawal. Drug cessation triggers a temporally orchestrated allostatic re-establishment of neuronal systems, which is manifested as opposing physiological and psychological effects to those exhibited by acute drug intoxication. Some withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea) resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can linger for months, and some adaptations, such as learned associations, may be established for life. We will briefly discuss the cellular mechanisms and neural circuitry that contribute to the opioid drug-dependent state, inferring an emerging role for neuroinflammation. We will argue that opioid addictive behaviors result from a learned relationship between opioids and relief from an existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a future stressful life event can recall the memory that opioid drugs alleviate negative affect (despair, sadness, and anxiety) and thereby precipitate craving, resulting in relapse. A learned association of relief of aversive states would fuel drug craving in vulnerable people living in an increasingly stressful society. We suggest that this route to addiction is contributive to the current opioid epidemic in the USA.

Accumbal Neural Responses During the Initiation and Maintenance of Intravenous Cocaine Self-Administration

2004 ◽  
Vol 91 (1) ◽  
pp. 314-323 ◽  
Author(s):  
Laura L. Peoples ◽  
Kevin G. Lynch ◽  
Jamie Lesnock ◽  
Nidhi Gangadhar
Keyword(s):  
Drug Effects ◽  
Extracellular Recording ◽  
Neural Responses ◽  
Self Administration ◽  
Drug Seeking ◽  
Recording Session ◽  
Seeking Behavior ◽  
Excitatory Responses ◽  
Drug Free ◽  
Intravenous Cocaine

During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.

Risperidone-to-methylphenidate switch reaction in children: three cases

2007 ◽  
Vol 21 (2) ◽  
pp. 216-219 ◽  
Author(s):  
Osman Sabuncuoglu
Keyword(s):  
Adverse Reactions ◽  
Female Adolescent ◽  
Borderline Intellectual Functioning ◽  
Hyperactivity Disorder ◽  
Oppositional Defiant ◽  
Free Interval ◽  
Functional Regulation ◽  
Opposing Effects ◽  
Drug Free ◽  
Risperidone Treatment

As atypical antipsychotics are increasingly used in the treatment of childhood behavioural disorders either as monotherapy or in combination with other medications, there is a need to know more about their safety, in particular during switching to and from methylphenidate treatment, as antipsychotics and methylphenidate have opposing effects on dopaminergic neurotransmission. This report is about three cases of children who developed severe adverse reactions during switching from risperidone to methylphenidate. The first patient was a 6-year-old boy, diagnosed with attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). He developed severe hyperactivity and agitation on taking methylphenidate after the discontinuation of risperidone treatment. The second patient was a girl of 6, already on risperidone for ADHD and borderline intellectual functioning when referred. She displayed severe hyperactivity, agitation and irritability upon switching to methylphenidate medication. The third patient was a 15-year-old female adolescent with a similar clinical course as the previous patients. In all the cases described here, it is only with the discontinuation of methylphenidate that the adverse reactions resolved and readministration of methylphenidate in two patients did not produce any adverse effect after a drug-free interval. Functional regulation of certain neuroreceptors during risperidone treatment may lead to altered behavioural responses upon switching to methylphenidate. Thus, a drug-free interval is recommended in order to prevent adverse reactions.

Sudden Death Associated with Switching Monoamine Oxidase Inhibitors

1986 ◽  
Vol 20 (12) ◽  
pp. 954-956 ◽  
Author(s):  
Stephen R. Bazire
Keyword(s):  
Sudden Death ◽  
Monoamine Oxidase ◽  
Abrupt Change ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor ◽  
Monoamine Oxidase Inhibitors ◽  
Free Interval ◽  
Drug Free

A drug-free interval is often recommended when switching monoamine oxidase inhibitors, although the evidence firmly supporting this caution has been minimal. A case is reported where an abrupt change in monoamine oxidase inhibitor was followed by the death of a patient.

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