Morphine Inhibits Acetylcholine Release in Rat Prefrontal Cortex When Delivered Systemically or by Microdialysis to Basal Forebrain

2005 ◽  
Vol 103 (4) ◽  
pp. 779-787 ◽  
Author(s):  
Nadir I. Osman ◽  
Helen A. Baghdoyan ◽  
Ralph Lydic
Keyword(s):  
Prefrontal Cortex ◽  
Basal Forebrain ◽  
Acetylcholine Release ◽  
Sprague Dawley ◽  
Guide Cannula ◽  
Microdialysis Probe ◽  
Prefrontal Cortical ◽  
Substantia Innominata ◽  
Morphine Administration ◽  
Intravenous Morphine

Background Cortical acetylcholine originates in the basal forebrain and is essential for maintaining normal cognition and arousal. Morphine impairs these cholinergically mediated cortical functions. The current study tested the hypothesis that morphine decreases prefrontal cortical acetylcholine release by acting at the level of the basal forebrain. Methods Adult male Sprague-Dawley rats (n = 18) were anesthetized with isoflurane. One microdialysis probe was placed in the substantia innominata region of the basal forebrain and perfused with Ringer's solution (control) followed by one concentration of morphine (1, 10, 100, or 1,000 microm) or morphine (1,000 microm) plus naloxone (100 microm). A second microdialysis probe was placed in the prefrontal cortex for measuring acetylcholine. In a second series of experiments, rats (n = 6) were implanted with electrodes for recording states of arousal, a guide cannula positioned above the prefrontal cortex for inserting a microdialysis probe, and an indwelling jugular vein catheter. The effects of administering intravenous morphine (30 mg/kg) versus normal saline (0.9%) on prefrontal cortical acetylcholine release, cortical electroencephalographic power, and behavior were quantified. Results Dialysis delivery of morphine to the substantia innominata caused a concentration-dependent, naloxone-sensitive decrease in acetylcholine release within the prefrontal cortex. The maximal decrease in acetylcholine was 36.3 +/- 11.5%. Intravenous morphine administration significantly decreased cortical acetylcholine release, increased electroencephalographic power in the 0.5- to 5-Hz range, and eliminated normal wakefulness. Conclusion Morphine causes obtundation of arousal and may cause cognitive impairment by acting at the level of the substantia innominata to disrupt cortical cholinergic neurotransmission.

scholarly journals Buprenorphine Disrupts Sleep and Decreases Adenosine Concentrations in Sleep-regulating Brain Regions of Sprague Dawley Rat

2011 ◽  
Vol 115 (4) ◽  
pp. 743-753 ◽  
Author(s):  
Elizabeth A. Gauthier ◽  
Sarah E. Guzick ◽  
Chad M. Brummett ◽  
Helen A. Baghdoyan ◽  
Ralph Lydic
Keyword(s):  
Eye Movement ◽  
Opioid Receptor ◽  
Reticular Formation ◽  
Basal Forebrain ◽  
Sleep Onset ◽  
Brain Regions ◽  
Pontine Reticular Formation ◽  
Sprague Dawley ◽  
Indwelling Catheter ◽  
Substantia Innominata

Background Buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine concentrations in regions of the basal forebrain and pontine brainstem that regulate sleep. Methods Male Sprague Dawley rats were implanted with intravenous catheters and electrodes for recording states of wakefulness and sleep. Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter and sleep-wake states were recorded for 24 h. In additional rats, buprenorphine was delivered by microdialysis to the pontine reticular formation and substantia innominata of the basal forebrain while adenosine was simultaneously measured. Results An antinociceptive dose of buprenorphine caused a significant increase in wakefulness (25.2%) and a decrease in nonrapid eye movement sleep (-22.1%) and rapid eye movement sleep (-3.1%). Buprenorphine also increased electroencephalographic delta power during nonrapid eye movement sleep. Coadministration of the sedative-hypnotic eszopiclone diminished the buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine significantly decreased adenosine concentrations in the pontine reticular formation (-14.6%) and substantia innominata (-36.7%). Intravenous administration of buprenorphine significantly decreased (-20%) adenosine in the substantia innominata. Conclusions Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset. These disruptions in sleep architecture were mitigated by coadministration of the nonbenzodiazepine sedative-hypnotic eszopiclone. The buprenorphine-induced decrease in adenosine concentrations in basal forebrain and pontine reticular formation is consistent with the interpretation that decreasing adenosine in sleep-regulating brain regions is one mechanism by which opioids disrupt sleep.

scholarly journals Opioid-induced Decreases in Rat Brain Adenosine Levels Are Reversed by Inhibiting Adenosine Deaminase

2009 ◽  
Vol 111 (6) ◽  
pp. 1327-1333 ◽  
Author(s):  
Ariana M. Nelson ◽  
Alanna S. Battersby ◽  
Helen A. Baghdoyan ◽  
Ralph Lydic
Keyword(s):  
Rat Brain ◽  
Adenosine Deaminase ◽  
Reticular Formation ◽  
Basal Forebrain ◽  
Brain Regions ◽  
Pontine Reticular Formation ◽  
Microdialysis Probe ◽  
Ringer’S Solution ◽  
Substantia Innominata ◽  
Adenosine Agonists

Background Opioids disrupt sleep and adenosine promotes sleep, but no studies have characterized the effects of opioids on adenosine levels in brain regions known to regulate states of arousal. Delivering opioids to the pontine reticular formation (PRF) and substantia innominata (SI) region of the basal forebrain disrupts sleep. In contrast, administering adenosine agonists to the PRF or SI increases sleep. These findings encouraged the current study testing the hypothesis that microdialysis delivery of opioids to the PRF or SI decreases adenosine levels in the PRF or SI, respectively. Methods A microdialysis probe was placed in the PRF of isoflurane anesthetized rats and perfused with Ringer's solution (control) followed by Ringer's solution containing morphine (0, 10, 30, 100, or 300 microm), fentanyl (100 microm), morphine (100 microm) and the adenosine deaminase inhibitor EHNA (100 microm), or naloxone (10 microm) and morphine (100 microm). Additional experiments measured adenosine levels in the SI before and during microdialysis delivery of morphine, fentanyl, and morphine plus EHNA. Results Morphine caused a significant (P < 0.05) concentration-dependent decrease in PRF adenosine levels. The significant decrease (-20%) in adenosine caused by 100 microm morphine was blocked by coadministration of naloxone. Fentanyl also significantly decreased (-13.3%) PRF adenosine. SI adenosine levels were decreased by morphine (-26.8%) and fentanyl (-27.4%). In both PRF and SI, coadministration of morphine and EHNA prevented the significant decrease in adenosine levels caused by morphine alone. Conclusions These data support the interpretation that decreased adenosine levels in sleep-regulating brain regions may be one of the mechanisms by which opioids disrupt sleep.

scholarly journals The Role of Primate Prefrontal Cortex in Bias and Shift Between Visual Dimensions

2019 ◽  
Vol 30 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Farshad A Mansouri ◽  
Mark J Buckley ◽  
Daniel J Fehring ◽  
Keiji Tanaka
Keyword(s):  
Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Top Down ◽  
Attentional Processes ◽  
Prefrontal Cortical ◽  
Frontopolar Cortex ◽  
Dorsolateral Prefrontal ◽  
Cortical Regions ◽  
Visual Cortical ◽  
Bilateral Lesions

Abstract Imaging and neural activity recording studies have shown activation in the primate prefrontal cortex when shifting attention between visual dimensions is necessary to achieve goals. A fundamental unanswered question is whether representations of these dimensions emerge from top-down attentional processes mediated by prefrontal regions or from bottom-up processes within visual cortical regions. We hypothesized a causative link between prefrontal cortical regions and dimension-based behavior. In large cohorts of humans and macaque monkeys, performing the same attention shifting task, we found that both species successfully shifted between visual dimensions, but both species also showed a significant behavioral advantage/bias to a particular dimension; however, these biases were in opposite directions in humans (bias to color) versus monkeys (bias to shape). Monkeys’ bias remained after selective bilateral lesions within the anterior cingulate cortex (ACC), frontopolar cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), or superior, lateral prefrontal cortex. However, lesions within certain regions (ACC, DLPFC, or OFC) impaired monkeys’ ability to shift between these dimensions. We conclude that goal-directed processing of a particular dimension for the executive control of behavior depends on the integrity of prefrontal cortex; however, representation of competing dimensions and bias toward them does not depend on top-down prefrontal-mediated processes.

Reduced prefrontal cortical dopamine, but not acetylcholine, release in vivo after repeated, intermittent phencyclidine administration to rats

1998 ◽  
Vol 258 (3) ◽  
pp. 175-178 ◽  
Author(s):  
J.David Jentsch ◽  
Laura Dazzi ◽  
Jasmeer P. Chhatwal ◽  
Christopher D. Verrico ◽  
Robert H. Roth
Keyword(s):  
Acetylcholine Release ◽  
Prefrontal Cortical

scholarly journals Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during instructed threat of shock

2020 ◽  
Author(s):  
Jayne Morriss ◽  
Tiffany Bell ◽  
Nicolò Biagi ◽  
Tom Johnstone ◽  
Carien M. van Reekum
Keyword(s):  
Prefrontal Cortex ◽  
Anxiety Disorder ◽  
Intolerance Of Uncertainty ◽  
Neural Circuitry ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Prefrontal Cortical ◽  
Cortical Regions ◽  
Rostral Prefrontal Cortex ◽  
Threat Of Shock

AbstractHeightened responding to uncertain threat is associated with anxiety disorder pathology. Here, we sought to determine if individual differences in self-reported intolerance of uncertainty (IU) underlie differential recruitment of neural circuitry during instructed threat of shock (n = 42). During the task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings, skin conductance and functional magnetic resonance imaging was acquired. Overall, participants displayed greater amygdala activation to uncertain threat vs. safe cues, in the absence of an effect of IU. However, we found that high was associated with greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat vs safe cues. These findings suggest that, during instructed threat of shock, IU is specifically related, over trait anxiety, to activation in prefrontal cortical regions. Taken together, these findings highlight the potential of self-reported IU in identifying mechanisms that may be related to conscious threat appraisal and anxiety disorder pathology.

scholarly journals Prefrontal Cortical Response to Conflict during Semantic and Phonological Tasks

2007 ◽  
Vol 19 (5) ◽  
pp. 761-775 ◽  
Author(s):  
Hannah R. Snyder ◽  
Keith Feigenson ◽  
Sharon L. Thompson-Schill
Keyword(s):  
Prefrontal Cortex ◽  
Cognitive Control ◽  
Phonological Processing ◽  
Functional Organization ◽  
Inferior Frontal Gyrus ◽  
General Function ◽  
Left Inferior Frontal Gyrus ◽  
Domain Specific ◽  
Prefrontal Cortical ◽  
Specific Effects

Debates about the function of the prefrontal cortex are as old as the field of neuropsychology—often dated to Paul Broca's seminal work. Theories of the functional organization of the prefrontal cortex can be roughly divided into those that describe organization by process and those that describe organization by material. Recent studies of the function of the posterior, left inferior frontal gyrus (pLIFG) have yielded two quite different interpretations: One hypothesis holds that the pLIFG plays a domain-specific role in phonological processing, whereas another hypothesis describes a more general function of the pLIFG in cognitive control. In the current study, we distinguish effects of increasing cognitive control demands from effects of phonological processing. The results support the hypothesized role for the pLIFG in cognitive control, and more task-specific roles for posterior areas in phonology and semantics. Thus, these results suggest an alternative explanation of previously reported phonology-specific effects in the pLIFG.

scholarly journals Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects

2019 ◽  
Vol 45 (4) ◽  
pp. 694-702 ◽  
Author(s):  
Nicholas L. Balderston ◽  
Emily M. Beydler ◽  
Camille Roberts ◽  
Zhi-De Deng ◽  
Thomas Radman ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Transcranial Magnetic Stimulation ◽  
Healthy Subjects ◽  
Magnetic Stimulation ◽  
Dorsolateral Prefrontal Cortex ◽  
Subcortical Structures ◽  
Prefrontal Cortical ◽  
Dorsolateral Prefrontal ◽  
Before And After ◽  
The Right

AbstractMuch of the mechanistic research on anxiety focuses on subcortical structures such as the amygdala; however, less is known about the distributed cortical circuit that also contributes to anxiety expression. One way to learn about this circuit is to probe candidate regions using transcranial magnetic stimulation (TMS). In this study, we tested the involvement of the dorsolateral prefrontal cortex (dlPFC), in anxiety expression using 10 Hz repetitive TMS (rTMS). In a within-subject, crossover experiment, the study measured anxiety in healthy subjects before and after a session of 10 Hz rTMS to the right dorsolateral prefrontal cortex (dlPFC). It used threat of predictable and unpredictable shock to induce anxiety and anxiety potentiated startle to assess anxiety. Counter to our hypotheses, results showed an increase in anxiety-potentiated startle following active but not sham rTMS. These results suggest a mechanistic link between right dlPFC activity and physiological anxiety expression. This result supports current models of prefrontal asymmetry in affect, and lays the groundwork for further exploration into the cortical mechanisms mediating anxiety, which may lead to novel anxiety treatments.

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