A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function.


:Previous studies have shown that chronic morphine increases levels of the G-protein subunits Gia and Goa, adenylate cyclase, cyclic AMP-dependent protein kinase, and certain phosphoproteins in the rat locus coeruleus, but not in several other brain regions studied, and that chronic morphine decreases levels of Gia and increases levels of adenylate cyclase in dorsal root ganglion/spinal cord (DRG-SC) co-cultures. These findings led us to survey the effects of chronic morphine on the G-protein/cyclic AMP system in a large number of brain regions to determine how widespread such regulation might be. We found that while most regions showed no regulation in response to chronic morphine, nucleus accumbens (NAc) and amygdala did show increases in adenylate cyclase and cyclic AMP-dependent protein kinase activity, and thalamus showed an increase in cyclic AMP-dependent protein kinase activity only. An increase in cyclic AMP-dependent protein kinase activity was also observed in DRG-SC co-cultures. Morphine regulation of G-proteins was variable, with decreased levels of Gia seen in the NAc, increased levels of Gia and Goa in amygdala, and no change in thalamus or the other brain regions studied. Interestingly, chronic treatment of rats with cocaine, but not with several non-abused drugs, produced similar changes compared to morphine in G-proteins, adenylate cyclase, and cyclic AMP-dependent protein kinase in the NAc, but not in the other brain regions studied. These results indicate that regulation of the G-protein/cyclic AMP system represents a mechanism by which a number of opiate-sensitive neurons adapt to chronic morphine and thereby develop aspects of opiate tolerance and/or dependence. The findings that chronic morphine and cocaine produce similar adaptations in the NAc, a brain region important for the reinforcing actions of many types of abused substances, suggest further that common mechanisms may underlie psychological aspects of drug addiction mediated by this brain region.


Brain Res


Brain research


Terwilliger RZ,Beitner-Johnson D,Sevarino KA,Crain SM,Nestler EJ




Has Abstract


1991-05-10 00:00:00














  • Excitation of Limulus photoreceptors by hydrolysis-resistant analogs of cGMP and cAMP.

    abstract::cGMP was proposed to be the agent which directly opens the light-sensitive channel in Limulus ventral photoreceptors. However, the light-sensitive rhabdomeral-lobe (R-lobe) is not uniformly responsive to cGMP injection; that is, there are 'hot spots' of sensitivity. A potent phosphodiesterase which rapidly hydrolyses ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Feng JJ,Frank TM,Fein A

    更新日期:1991-06-28 00:00:00

  • Distribution of vestibulospinal contacts on the dendrites of ipsilateral splenius motoneurons: an anatomical substrate for push-pull interactions during vestibulocollic reflexes.

    abstract::Excitatory and inhibitory synapses may control neuronal output through a push-pull mechanism--that is, increases in excitation are coupled to simultaneous decreases in inhibition or vice versa. This pattern of activity is characteristic of excitatory and inhibitory vestibulospinal axons that mediate vestibulocollic re...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Grande G,Bui TV,Rose PK

    更新日期:2010-05-28 00:00:00

  • Dexamethasone and forskolin synergistically increase [Met5]enkephalin accumulation in mixed brain cell cultures.

    abstract::Possible synergistic effects of the glucocorticoid dexamethasone (DEX, 10(-7) M) and the adenylate cyclase agonist forskolin (FSK, 10(-5) M) on [Met5]enkephalin (ME) accumulation were examined in enriched rat glial cultures and in mixed neuronal/glial cultures. In enriched glial cultures, DEX and FSK each stimulated t...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: McMillian MK,Pennypacker KR,Thai L,Wu GC,Suh HH,Simmons KL,Hudson PM,Sawin SB,Hong JS

    更新日期:1996-08-19 00:00:00

  • Adrenergic innervation in the tibial and vagus nerves of rats with streptozotocin-induced diabetes.

    abstract::Adrenergic innervation of tibial and vagus nerves was studied after 1-16 weeks duration of streptozotocin (STZ)-induced diabetes in rats. Sucrose-phosphate glyoxylic acid (SPG) histochemistry and the formaldehyde-induced fluorescence (FIF) method were used to demonstrate adrenergic nerve fibers in the epi-perineurial ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Koistinaho J,Wadhwani KC,Rapoport SI

    更新日期:1990-04-09 00:00:00

  • Evidence to suggest that extracellular acetate is accumulated by rat hippocampal cholinergic nerve terminals for acetylcholine formation and release.

    abstract::It is well established that extracellular choline is transported into central cholinergic nerve terminals by 'high' and 'low' affinity processes to form the neurotransmitter acetylcholine (ACh). The intent of the present investigation was to ascertain whether extracellular acetate might also be transported into centra...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Carroll PT

    更新日期:1997-04-04 00:00:00

  • NMDA-receptor mediated electrical epileptogenesis in the organotypic culture of rat hippocampus.

    abstract::Extracellular field recordings were made in CA1 in the hippocampal explant cultures in oxygenated artificial cerebrospinal fluid. Schaffer collaterals were stimulated with 1-s trains of 60 Hz pulses every 10 min. Seizures were reliably elicited with progressive lengthening over 1-2 h. D-APV, an N-methyl-D-aspartate (N...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Shin C,Tamaki Y,Wilson JT,Butler L,Sakaguchi T

    更新日期:1992-08-28 00:00:00

  • Peripheral maps and synapse elimination in the cerebellum of the rat. II. Representation of peripheral inputs through the climbing fiber pathway in the posterior vermis of X-irradiated adult rats.

    abstract::The present study gives a detailed description of the functional characteristics and of the topographic distribution of responses mediated through the climbing fiber (CF) pathway in the cerebellum of adult rats which have been repeatedly irradiated from birth so that the Purkinje cells (PCs) in the adult remained inne...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Mariani J,Mulle C,Geoffroy B,Delhaye-Bouchaud N

    更新日期:1987-09-22 00:00:00

  • Release of amino acids from the maturing cobalt-induced epileptic focus.

    abstract::A study was made of the release of excitatory, inhibitory and other amino acids from epileptic foci induced in the sensorimotor cortex of rats by cobalt implantation. A new in vivo superfusion method was employed which gives free movement to the animals and allows study over periods of days and weeks. Most amino acids...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Dodd PR,Bradford HF

    更新日期:1976-07-30 00:00:00

  • Structure and function of urodele myelin lacking alpha-hydroxy fatty acid-containing galactosphingolipids: slow nerve conduction and unusual myelin thickness.

    abstract::Myelin of several Caudata (Urodela) species appears to be unique in the fact that it lacks hydroxycerebrosides and hydroxysulfatides although it contains their non-hydroxy counterparts. Comparison of the nerve conduction velocities in the Urodeles Necturus (salamander) and Notophthalmus (newt) with that in a reptile, ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Ki PF,Kishimoto Y,Lattman EE,Stanley EF,Griffin JW

    更新日期:1985-10-14 00:00:00

  • Glucose/oxygen deprivation induces the alteration of synapsin I and phosphosynapsin.

    abstract::Synapsin I is believed to be involved in regulating neurotransmitter release and in synapse formation. Its interactions with the actin filaments and synaptic vesicles are regulated by phosphorylation. Because exocytosis and synapsin I phosphorylation are a Ca(2+)-dependent process, it is possible that an ischemic insu...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Jung YJ,Park SJ,Park JS,Lee KE

    更新日期:2004-01-16 00:00:00

  • Behavioral effects of CD40-CD40L pathway disruption in aged PSAPP mice.

    abstract::We have shown that, when an amyloid-beta peptide (Abeta) overproducing transgenic mouse model (PSAPP) of Alzheimer's disease (AD) is treated with a depleting antibody against CD40L, it causes marked attenuation of Abeta pathology associated with decreased amyloidogenic processing of amyloid precursor protein (APP) and...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Todd Roach J,Volmar CH,Dwivedi S,Town T,Crescentini R,Crawford F,Tan J,Mullan M

    更新日期:2004-07-23 00:00:00

  • Behavioral sensitization to cocaine: modulation by the cyclic AMP system in the nucleus accumbens.

    abstract::We have previously observed that chronic cocaine administration increases levels of adenylyl cyclase and cAMP-dependent protein kinase (PKA) in the nucleus accumbens (NAc). In the present work we directly examined the involvement of the cAMP system at the level of the NAc in cocaine-induced locomotor activity and sens...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Miserendino MJ,Nestler EJ

    更新日期:1995-03-20 00:00:00

  • Cholinergic modulation of neocortical long-term potentiation in the awake, freely moving rat.

    abstract::The neocortex has proven resistant to LTP induction using standard in vitro and acute, in vivo preparations. Because the neocortex is widely thought to be involved in long-term information storage, this resistance raises questions about the validity of LTP as a memory model. Recently, we have shown that the neocortex ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Boyd TE,Trepel C,Racine RJ

    更新日期:2000-10-20 00:00:00

  • Brain laterality as a determinant of susceptibility to depression in an animal model.

    abstract::Rats exposed to stressors that cannot be controlled may develop a deficit in their ability to subsequently learn to control a new stressor. This phenomenon is known as 'learned helplessness' and is a well-accepted animal model of depression. Evidence is presented showing that rats having different directional biases o...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Carlson JN,Glick SD

    更新日期:1991-06-07 00:00:00

  • The effects of (-)- and (+)-beta-cyclazocine on NMDA-evoked responses and NMDA-mediated cell damage in cultured rat hippocampal neurons.

    abstract::Microspectrofluorimetric measurements of excitatory amino acid-evoked rises in intracellular free calcium concentration ([Ca2+]i), electrophysiological measurements of currents through single NMDA receptor-operated ion channels and estimates of cellular viability following NMDA challenge were employed to examine the i...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Sawyer DC,McLarnon JG,Church J

    更新日期:1995-11-06 00:00:00

  • Enriched environment delays the onset of hippocampal damage after global cerebral ischemia in rats.

    abstract::An enriched environment has been shown to improve cognitive, behavioral and histopathological outcome after focal cerebral ischemia and head trauma. The purpose of this study was to determine the effect of an enriched environment on histopathology following global cerebral ischemia. Wistar rats (21 weeks of age) were ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Belayev A,Saul I,Liu Y,Zhao W,Ginsberg MD,Valdes MA,Busto R,Belayev L

    更新日期:2003-02-21 00:00:00

  • Increase in glutamate sensitivity of subthalamic nucleus neurons following bilateral decortication: a microiontophoretic study in the rat.

    abstract::Responses of subthalamic neurons (STN) to the iontophoretic application of glutamate (Glu), acetylcholine (ACh) and GABA were studied in rats 2 or 3 weeks following bilateral decortication, and were compared to those obtained in normal animals. All the cells recorded in lesioned rats showed a decrease in their spontan...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Rouzaire-Dubois B,Scarnati E

    更新日期:1987-02-17 00:00:00

  • Cytosolic phospholipase A2 (cPLA2) distribution in murine brain and functional studies indicate that cPLA2 does not participate in muscarinic receptor-mediated signaling in neurons.

    abstract::Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of membrane phospholipids and has been suggested as an effector in the receptor-mediated release of arachidonic acid in signal transduction. The potential role of cPLA2 as an effector in muscarinic acetylcholi...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Lautens LL,Chiou XG,Sharp JD,Young WS 3rd,Sprague DL,Ross LS,Felder CC

    更新日期:1998-10-26 00:00:00

  • Distribution of CaMKIIα expression in the brain in vivo, studied by CaMKIIα-GFP mice.

    abstract::To facilitate the study of the CaMKIIα function in vivo, a CaMKIIα-GFP transgenic mouse line was generated. Here, our goal is to provide the first neuroanatomical characterization of GFP expression in the CNS of this line of mouse. Overall, CaMKIIα-GFP expression is strong and highly heterogeneous, with the dentate gy...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Wang X,Zhang C,Szábo G,Sun QQ

    更新日期:2013-06-26 00:00:00

  • The distribution of normal brain water content in Wistar rats and its increase due to ischemia.

    abstract::The aim of this study was to describe the normal distribution of the water content in several regions of the rat brain and furthermore to determine if global ischemia results in a variable increase in water content in these regions. Water content was determined in 40 regions; in 8 unaffected brains by gravimetry and i...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Schwab M,Bauer R,Zwiener U

    更新日期:1997-02-21 00:00:00

  • Acetylcholine sensitivity in sensory neurons dissociated from the cat petrosal ganglion.

    abstract::The petrosal ganglia contain the somata of the sensory fibers of the glossopharyngeal nerves, innervating structures of the tongue, pharynx, carotid sinus and carotid body. Petrosal ganglia were excised from adult cats and their neurons were dissociated and kept in tissue culture for 7-12 days. Intracellular recording...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Varas R,Alcayaga J,Zapata P

    更新日期:2000-11-03 00:00:00

  • Alterations of adenylyl cyclase-coupled growth hormone-releasing hormone (GHRH) pituitary receptors in different conditions of GHRH deprivation.

    abstract::Previous studies have clearly shown that the progressive decrease of growth hormone (GH) secretion occurring during ageing is coupled with a reduced responsiveness of pituitary GHRH receptors both in terms of GH secretion and activation of the adenylyl cyclase (AC), in the presence of increased basal values of the enz...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Qing Y,Parenti M,Guzzi F,Ceresoli G,Müller EE,Cocchi D

    更新日期:1994-04-25 00:00:00

  • Anti-seizure and anti-epileptogenic effect of gamma-vinyl gamma-aminobutyric acid in amygdaloid kindling.

    abstract::We examined the effects of systemic administration of gamma-vinyl gamma-aminobutyric acid (GVG), a gamma-aminobutyric acid (GABA) transaminase inhibitor, on the kindling model of epilepsy in rats. GVG (1200 or 1500 mg/kg) approximately doubled the number of stimulations required for kindling development. GVG also supp...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Shin C,Rigsbee LC,McNamara JO

    更新日期:1986-11-29 00:00:00

  • Developmental sequence in the origin of descending spinal pathways. Studies using retrograde transport techniques in the North American opossum (Didelphis virginiana).

    abstract::The origin of descending pathways to thoracic and cervical levels of the spinal cord has been investigated with retrograde tracing techniques in a series of pouch young and adult opossums. The opossum was chosen because it is born in a very immature state, 12-13 days after conception, and has a protracted development ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Cabana T,Martin GF

    更新日期:1984-08-01 00:00:00

  • Differential distribution of S100 protein and calretinin in mechanosensory and chemosensory cells of adult zebrafish (Danio rerio).

    abstract::Calcium-binding proteins play a critical role in vertebrate sensory cells, and some of them have been detected in mechanosensory and chemosensory cells of bony and cartilaginous fishes. In this study immunohistochemistry and Western blot were used to investigate the occurrence and the distribution of S100 protein and ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Germanà A,Paruta S,Germanà GP,Ochoa-Erena FJ,Montalbano G,Cobo J,Vega JA

    更新日期:2007-08-08 00:00:00

  • Loss of entrainment and anatomical plasticity after lesions of the hamster retinohypothalamic tract.

    abstract::The suprachiasmatic nuclei receive photic input information directly through a retinohypothalamic tract (RHT) and indirectly through a projection from the intergeniculate leaflet of the lateral geniculate complex, the geniculohypothalamic tract (GHT). Prior work has established that the RHT is sufficient for entrainme...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Johnson RF,Moore RY,Morin LP

    更新日期:1988-09-20 00:00:00

  • Characterizing the neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity.

    abstract::Lycium barbarum is an oriental medicinal herb that has long been used for its anti-aging and cell-protective properties. Previous studies have shown that aqueous extracts from L. barbarum exhibit neuroprotection via inhibiting pro-apoptotic signaling pathways. Other active components can also be accomplished by novel ...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Ho YS,Yu MS,Lai CS,So KF,Yuen WH,Chang RC

    更新日期:2007-07-16 00:00:00

  • Localization of the NBMPR-sensitive equilibrative nucleoside transporter, ENT1, in the rat dorsal root ganglion and lumbar spinal cord.

    abstract::ENT1 is an equilibrative nucleoside transporter that enables trans-membrane bi-directional diffusion of biologically active purines such as adenosine. In spinal cord dorsal horn and in sensory afferent neurons, adenosine acts as a neuromodulator with complex pro- and anti-nociceptive actions. Although uptake and relea...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Governo RJ,Deuchars J,Baldwin SA,King AE

    更新日期:2005-10-19 00:00:00

  • Neurodegeneration in autoimmune MRL-lpr mice as revealed by Fluoro Jade B staining.

    abstract::As in many humans suffering from lupus erythematosus, the development of systemic autoimmunity and inflammation in Fas-deficient MRL-lpr mice is accompanied by CNS dysfunction of unknown etiology. Experimental studies revealed infiltration of lymphoid cells into the choroid plexus, reduced neuronal complexity, retarde...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Ballok DA,Millward JM,Sakic B

    更新日期:2003-02-28 00:00:00

  • Non-dopaminergic nigrostriatal pathway.

    abstract::The nigrostriatal projection was studied with a retrograde tracing method (Evans blue, EB) combined with a technique for dopamine histofluorescence. The study, realized in control rats and in animals with 6-hydroxydopamine-induced lesions of the dopaminergic pathway, yielded the following results. (1) In 3 control rat...

    journal_title:Brain research

    pub_type: 杂志文章


    authors: Guyenet PG,Crane JK

    更新日期:1981-06-01 00:00:00