Selective Effects of the Endogenous Cannabinoid Arachidonylethanolamide (Anandamide) on Regional Cerebral Blood Flow in the Rat

Stein, Elliot A.; Fuller, Scott A.; Edgemond, William S.; Campbell, William B.

doi:10.1016/s0893-133x(98)00043-8

Cited by 31 publications

(30 citation statements)

References 58 publications

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“…14 C]iodoantipyrene Imaging cocaine sensitization in awake rats M Febo et al autoradiography have shown cocaine-induced elevations in regions cerebral blood flow (Stein and Fuller, 1992). Increased flow of oxygenated blood to regions of enhanced neuronal activity and metabolism likely contributes to alterations in BOLD observed in this study and Febo et al (2004).…”

Section: Discussionmentioning

confidence: 58%

“…Increased oxygenation of these areas contributes to the elevations in BOLD signal intensity (Thompson et al, 2003). An acute cocaine injection increases cerebral metabolic activity (Porrino, 1993) and blood flow (Stein and Fuller, 1992); effects that are likely to contribute to changes in BOLD signal intensity (Febo et al, 2004). These alterations could possibly involve effects of cocaine on synaptic monoamine levels throughout cortical and subcortical structures (Goeders and Smith, 1983;Kalivas and Duffy, 1993).…”

Section: Introductionmentioning

confidence: 99%

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The Neural Consequences of Repeated Cocaine Exposure Revealed by Functional MRI in Awake Rats

Febo

Segarra

Nair

et al. 2004

Neuropsychopharmacol

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The use of functional magnetic resonance imaging (fMRI) in animal models of cocaine addiction is an invaluable tool for investigating the neuroadaptations that lead to this psychiatric disorder. We used blood-oxygen-level-dependent (BOLD) MRI in awake rats to identify the neuronal circuits affected by repeated cocaine administration. Rats were given an injection of cocaine (15 mg/kg, i.p.) or its vehicle for 7 days, abstained from injections for 1 week, and challenged with an intracerebroventricular cocaine injection during functional imaging. Acute cocaine produced robust positive BOLD responses across well-known monoamine-enriched brain regions, such as the prefrontal cortex, nucleus accumbens, dorsal striatum, sensory cortex, hippocampus, thalamus, and midbrain areas. However, repeated cocaine administration resulted in lower BOLD responses in the prefrontal cortex, agranular insular cortex, nucleus accumbens, ventral pallidum, and dorsomedial thalamus, among other brain regions. Reductions in BOLD intensity were not associated with variations in cerebrovascular reactivity between drug naïve rats and those repeatedly exposed to cocaine. Therefore, the lower metabolic activation in response to cocaine could reflect a reduced neuronal and/or synaptic activity upon repeated administration.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

The Neural Consequences of Repeated Cocaine Exposure Revealed by Functional MRI in Awake Rats

Febo

Segarra

Nair

et al. 2004

Neuropsychopharmacol

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“…In the present study, the effects of AEA on calcium and potassium channels would appear to be limited, since the major physiologic change produced by these actions, vasorelaxation and a decrease in systemic vascular resistance (Garcia et al 2001), require doses significantly higher than those used to block APO-induced stereotypy. Similarly, large changes in calcium and potassium conductance in basal ganglia neurons or local cerebral blood vessels might be expected to cause marked effects on cerebral blood flow or basal ganglia function: effects that are not observed at the highest dose used in this study (Stein et al 1998; present data). Thus, although there is evidence for interactions among AEA, calcium, and potassium chan- and biting (b), licking (c), and sniffing (d) stereotypies.…”

Section: The Specificity Of the Effects Of Carb And Aea On Electrotonmentioning

confidence: 54%

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

Moore

Grace

2002

Neuropsychopharmacology

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Stimulation of dopamine (DA) receptors in the striatum evokes a number of alterations in motor behavior in rats, as well as causing several alterations in cellular physiology, including changes in membrane potential, cell excitability, afferent drive, and electrotonic coupling. One cellular property that is potently modulated by DA stimulation is electrotonic coupling, a process shown to subserve motor pattern generation. To examine whether electrotonic coupling plays a role in mediating a specific set of DA receptor-mediated motor behaviors, we tested the effects of two inhibitors of gap junction conductance, carbenoxolone (CARB) and anandamide (AEA), on apomorphine (APO)-induced motor responses. We then used intra-striatal infusions of CARB to determine the role of electrotonic coupling specifically in the ventral striatum in the expression of i.p.) significantly increased motor activity (a composite score) and the frequencies of oral and sniffing stereotypies. APO also disrupted grooming initiation and completion. APO-induced oral stereotypies were selectively blocked by systemic administration of CARB (7.0, 35.0 mg/kg Adaptive behaviors, both learned and spontaneous, consist of sequences of "micro" movements executed by closely-related muscle groups. There is evidence that the initiation and execution of individual movements, such as oral movements involved in feeding, as well as the linking of these movements into a behavioral sequence, depend upon neuronal networks within the Beninger et al. 1991;Braun and Chase 1986;Byrnes et al. 1994;Delfs and Kelley 1990). Thus, in the context of behavioral sequencing, the simple 'repetitive' stereotypy (Berridge and Aldridge 2000a) produced by D2 receptor over-stimulation in the striatum (Delfs and Kelley 1990) can be seen as the inability to release one 'simple' behavior in order to allow initiation of the next simple behavior in a normal, adaptive sequence (Pedro et al. 1994;Szechtman et al. 1999). One means by which neuronal networks may interact within the striatum is via communication among clusters of functionally related striatal neurons. Such a network interaction may be mediated via gap junctions. It is well-established that electrotonic transmission between developing neurons is important in the formation and stabilization of functional networks (Bannerman et al. 2000;Peinado et al. 1993;Roerig and Feller 2000). However, there is also evidence that in the adult brain, electrotonic coupling directly mediates forms of neuronal network activity (Bou-Flores and Berger 2001;Jefferys 1995;Perez Velazquez and Carlen 2000) which, in turn, contribute to rhythmic behavioral patterning (Bou-Flores and Berger 2001;Rothwell 1998). Thus, it is likely that motor patterning may involve activity within neuronal networks coordinated via gap junctions. In the striatum, cells express connexins, the protein building blocks of gap junctions (Belluardo et al. 2000;Bennett et al. 1999). Striatal neurons also exhibit dye coupling, the transfer of dye molecules between neurons thro...

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“…Limbic activation has indeed been demonstrated in four animal studies (58)(59)(60)(61) and in a recent human study using functional MRI (62). Cocaine's rapid temporal dynamics (63) and/or local vasoconstrictive actions may have prevented a demonstration of limbic effects in several other studies (64-69).…”

Section: Discussionmentioning

confidence: 85%

Limbic Activation During Cue-Induced Cocaine Craving

Childress

Mozley²,

McElgin³

et al. 1999

AJP

1,372

978

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Objective-Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans.Method-Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions.Results-During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the nondrug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex).Conclusions-These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.Craving for a drug is a cardinal feature of addictive disorders and is clinically significant because of its potential to trigger drug use and relapse (1). The cocaine epidemic in the United States has prompted an intensive, largely unsuccessful search for medications to treat cocaine craving (2,3). This search has likely been complicated by a heterogeneous target: drug desire that emerges during cocaine cessation (4) may well have a different brain substrate than desire induced by cocaine itself (5) and the cues that signal it (6). Noninvasive brain imaging studies have recently begun to examine the brain substrates of both withdrawal-based craving (7,8) and cue-induced craving (9-11) in humans. We present here a hypothesis-guided imaging study of cue-induced cocaine craving in which we used evocative video cues from our prior work, which measured peripheral and subjective correlates of that state (6,(12)(13)(14).Human cocaine users often experience profound desire for the drug when they encounter cues (people, places, paraphernalia, etc.) associated with cocaine (6,15). Cue-induced cocaine craving is sometimes accompanied by a number of signs and symptoms similar to the effects Address reprint requests to Dr. Childress, Addiction Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, 3900 Chestnut St., Philadelphia, PA 19104; childress@research.trc.upenn.edu.. Data presented in part at meetings of the Society for Neurosciences, the College on Problems of Drug Dependence, the American Psychiatric Association, and the American College of Neuropsychopharmacology (1994Neuropsychopharmacology ( -1997 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript of cocaine itself, including generalized arousal, palpitations, light-head...

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Selective Effects of the Endogenous Cannabinoid Arachidonylethanolamide (Anandamide) on Regional Cerebral Blood Flow in the Rat

Cited by 31 publications

References 58 publications

The Neural Consequences of Repeated Cocaine Exposure Revealed by Functional MRI in Awake Rats

The Neural Consequences of Repeated Cocaine Exposure Revealed by Functional MRI in Awake Rats

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

Limbic Activation During Cue-Induced Cocaine Craving

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