Search Results - (Author, Cooperation:G. F. Koob)
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1Latest Papers from Table of Contents or Articles in PressF. S. Collins ; J. M. Anderson ; C. P. Austin ; J. F. Battey ; L. S. Birnbaum ; J. P. Briggs ; J. A. Clayton ; B. Cuthbert ; R. W. Eisinger ; A. S. Fauci ; J. I. Gallin ; G. H. Gibbons ; R. I. Glass ; M. M. Gottesman ; P. A. Gray ; E. D. Green ; F. B. Greider ; R. Hodes ; K. L. Hudson ; B. Humphreys ; S. I. Katz ; G. F. Koob ; W. J. Koroshetz ; M. S. Lauer ; J. R. Lorsch ; D. R. Lowy ; J. J. McGowan ; D. M. Murray ; R. Nakamura ; A. Norris ; E. J. Perez-Stable ; R. I. Pettigrew ; W. T. Riley ; G. P. Rodgers ; P. A. Sieving ; M. J. Somerman ; C. Y. Spong ; L. A. Tabak ; N. D. Volkow ; E. L. Wilder
American Association for the Advancement of Science (AAAS)
Published 2016Staff ViewPublication Date: 2016-03-26Publisher: American Association for the Advancement of Science (AAAS)Print ISSN: 0036-8075Electronic ISSN: 1095-9203Topics: BiologyChemistry and PharmacologyComputer ScienceMedicineNatural Sciences in GeneralPhysicsKeywords: Animals ; Biomedical Research/*economics ; Humans ; National Institutes of Health (U.S.)/*economicsPublished by: -
2Articles: DFG German National LicensesParsons, L. H. ; Caine, S. B. ; Sokoloff, P. ; Schwartz, J.-C. ; Koob, G. F. ; Weiss, F.
Oxford, UK : Blackwell Science Ltd
Published 1996Staff ViewISSN: 1471-4159Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Abstract: The mechanism by which two D3 receptor-preferring agonists, 7-hydroxydipropylaminotetralin (7-OH-DPAT) and quinelorane, modulate cocaine reinforcement was examined by monitoring nucleus accumbens dopamine levels with in vivo microdialysis while rats intravenously self-administered the following four different drug solutions consecutively: (1) cocaine; (2) a combination of cocaine plus a low dose of either agonist; (3) either agonist alone; and finally, (4) a physiological saline solution. Both 7-OH-DPAT (4 µg/infusion) and quinelorane (0.25 µg/infusion) decreased cocaine (0.25 mg/infusion) intake in a manner indicating an enhancement of cocaine reinforcement and simultaneously decreased the cocaine-induced elevations in nucleus accumbens dopamine levels by 〉50%. Subsequent self-administration of either 7-OH-DPAT (4 µg/infusion) or quinelorane (0.25 µg/infusion) alone resulted in significant, but stable, increases in drug intake, with a concurrent decrease in nucleus accumbens dopamine levels to ∼50% below nondrug baseline levels. These findings indicate that postsynaptic D3 receptor stimulation in the nucleus accumbens enhances the reinforcing properties of cocaine. In a second experiment, local application of 7-OH-DPAT via reverse dialysis (30 and 100 nM perfusate concentrations) dose-dependently decreased nucleus accumbens dopamine efflux to 76 ± 3.9 and 61 ± 6.3% of baseline, respectively, whereas there was no effect of this agonist on dopamine efflux in the ipsilateral striatum of these same animals. Coperfusion with the D3 receptor-preferring antagonist nafadotride dose-dependently blocked the effect of 7-OH-DPAT on nucleus accumbens dopamine efflux. These results suggest that, at low concentrations, 7-OH-DPAT selectively activates D3 receptors in vivo.Type of Medium: Electronic ResourceURL: -
3Articles: DFG German National LicensesMENZAGHI, F. ; RASSNICK, S. ; HEINRICHS, S. ; BALDWIN, H. ; PICH, E. M. ; WEISS, F. ; KOOB, G. F.
Oxford, UK : Blackwell Publishing Ltd
Published 1994Staff ViewISSN: 1749-6632Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: Natural Sciences in GeneralType of Medium: Electronic ResourceURL: -
4Articles: DFG German National LicensesCADOR, M. ; DUMAS, S. ; COLE, B. J. ; MALLET, J. ; KOOB, G. F. ; LE MOAL, M. ; STINUS, L.
Oxford, UK : Blackwell Publishing Ltd
Published 1992Staff ViewISSN: 1749-6632Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: Natural Sciences in GeneralType of Medium: Electronic ResourceURL: -
5Articles: DFG German National LicensesVallée, M. ; Shen, W. ; Heinrichs, S. C. ; Zorumski, C. F. ; Covey, D. F. ; Koob, G. F. ; Purdy, R. H.
Oxford, UK : Blackwell Science Ltd
Published 2001Staff ViewISSN: 1460-9568Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Pregnenolone sulphate (PREGS) has generated interest as one of the most potent memory-enhancing neurosteroids to be examined in rodent learning studies, with particular importance in the ageing process. The mechanism by which this endogenous steroid enhances memory formation is hypothesized to involve actions on glutamatergic and GABAergic systems. This hypothesis stems from findings that PREGS is a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of γ-aminobutyric acidA receptors (GABAARs). Moreover, PREGS is able to reverse the amnesic-like effects of NMDAR and GABAAR ligands. To investigate this hypothesis, the present study in rats examined the memory-altering abilities of structural analogs of PREGS, which differ in their modulation of NMDAR and/or GABAAR function. The analogs tested were: 11-ketopregnenolone sulphate (an agent that is inactive at GABAARs and NMDARs), epipregnanolone ([3β-hydroxy-5β-pregnan-20-one] sulphate, an inhibitor of both GABAARs and NMDARs), and a newly synthesized (–) PREGS enantiomer (which is identical to PREGS in effects on GABAARs and NMDARs). The memory-enhancing effects of PREGS and its analogs were tested in the passive avoidance task using the model of scopolamine-induced amnesia. Both PREGS and its (–) enantiomer blocked the effects of scopolamine. The results show that, unlike PREGS, 11-ketopregnenolone sulphate and epipregnanolone sulphate failed to block the effect of scopolamine, suggesting that altering the modulation of NMDA receptors diminishes the memory-enhancing effects of PREGS. Moreover, enantioselectivity was demonstrated by the ability of natural PREGS to be an order of magnitude more effective than its synthetic enantiomer in reversing scopolamine-induced amnesia. These results identify a novel neuropharmacological site for the modulation of memory processes by neuroactive steroids.Type of Medium: Electronic ResourceURL: -
6Articles: DFG German National LicensesStaff View
ISSN: 1749-6632Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: Natural Sciences in GeneralType of Medium: Electronic ResourceURL: -
7Articles: DFG German National LicensesStaunton, D. A. ; Magistretti, P. J. ; Koob, G. F. ; Shoemaker, W. J. ; Bloom, F. E.
[s.l.] : Nature Publishing Group
Published 1982Staff ViewISSN: 1476-4687Source: Nature Archives 1869 - 2009Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsNotes: [Auszug] Male Sprague-Dawley rats (Charles River Laboratories; mean weight 305 g) were used. To study denervation super-sensitivity, 8 jjig of 6-hydroxydopamine were injected into the nucleus accumbens on each side as previously described14. Sham-treated control subjects were prepared with bilateral ...Type of Medium: Electronic ResourceURL: -
8Articles: DFG German National LicensesKODA, L. Y. ; KOOB, G. F. ; SHIER, W. T. ; BLOOM, F. E.
[s.l.] : Nature Publishing Group
Published 1978Staff ViewISSN: 1476-4687Source: Nature Archives 1869 - 2009Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsNotes: [Auszug] We used male Sprague-Dawley rats (250-350 g); razor-blade slices of caudate nucleus were incubated for 30 min at 37 C with various compounds at 510-4M (refs 16-18). Tissues were then fixed with potassium permanganate and examined under the electron microscope19. After incubation with THP, small ...Type of Medium: Electronic ResourceURL: -
9Articles: DFG German National LicensesSchulteis, G. ; Ahmed, S. H. ; Morse, A. C. ; Koob, G. F. ; Everitt, B. J.
[s.l.] : Macmillan Magazines Ltd.
Published 2000Staff ViewISSN: 1476-4687Source: Nature Archives 1869 - 2009Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsNotes: [Auszug] The habitual behaviour of many opiate addicts means that the aversive symptoms of drug withdrawal are frequently experienced in specific environments. Stimuli in these environments acquire some of the negative affective properties of opiate withdrawal through pavlovian ...Type of Medium: Electronic ResourceURL: -
10Articles: DFG German National LicensesFray, P. J. ; Sahakian, B. J. ; Robbins, T. W. ; Koob, G. F. ; Iversen, S. D.
Springer
Published 1980Staff ViewISSN: 1432-2072Keywords: Rating scales ; Photocell activity cages ; Measurement ; Stereotypy ; d-Amphetamine ; Apomorphine ; Dopamine ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract A novel means of measuring and analysing behavioural effects of dopamine agonists is described and illustrated by a comparison of the effects of d-amphetamine and apomorphine in the rat. d-Amphetamine (0–15 mg/kg IP) produced significant dose- and time-dependent changes in responses such as locomotion, rearing and sniffing, but not in licking or gnawing. In contrast, apomorphine (0–5 mg/kg SC) produced significant increases in licking and gnawing, as well as in locomotion and sniffing, but no changes in rearing. The results are discussed in comparison with those obtained by other methods, such as photocell beam interruptions or stereotypy rating scales, and may be of importance in elucidating the functions of the forebrain dopamine projections.Type of Medium: Electronic ResourceURL: -
11Articles: DFG German National LicensesVaccarino, F. J. ; Bloom, F. E. ; Rivier, J. ; Vale, W. ; Koob, G. F.
[s.l.] : Nature Publishing Group
Published 1985Staff ViewISSN: 1476-4687Source: Nature Archives 1869 - 2009Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsNotes: [Auszug] Thirty-two male Wistar rats (250-300 g) were used and a 23-gauge guide cannula was implanted 1 mm dorsal to the right or left lateral ventricle of each rat (coordinates for the surgery using the Pellegrino and Cushman atlas8: 0.6 mm posterior to bregma, 2.0 mm lateral of the midline suture, 3.2 mm ...Type of Medium: Electronic ResourceURL: -
12Articles: DFG German National LicensesMoal, M. Le ; Koob, G. F. ; Koda, L. Y. ; Bloom, F. E. ; Manning, M. ; Sawyer, W. H. ; Rivier, J.
[s.l.] : Nature Publishing Group
Published 1981Staff ViewISSN: 1476-4687Source: Nature Archives 1869 - 2009Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsNotes: [Auszug] For measurements on blood pressure in conscious animals, Wistar rats (Charles River Farms, 300-400 g) were anaesthetized with halothane through an open face mask. The abdominal aorta was cannulated with PE 10 polyethylene tubing through the left femoral artery, and tied in place about 2.5 cm above ...Type of Medium: Electronic ResourceURL: -
13Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Conflict ; Ethanol ; Chlordiazepoxide ; FG 7142 ; RO 15-1788Source: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Previous results in our laboratory have shown that both chlordiazepoxide and ethanol will release punished responding in a rat operant conflict test using incremental shock. In the present study, a benzodiazepine antagonist and a benzodiazepine inverse agonist were used to explore the neurochemical basis for this behavioral action. N-methyl-β-carboline-3-carboxamide (FG 7142) at high doses (20 and 40 mg/kg) produced suppression of both punished and unpunished responding, and reversed the release of punished responding produced by both chlordiazepoxide and ethanol, but only at doses that produced an effect on its own. FG 7142 thus acted to oppose the actions of both ethanol and benzodiazepines but in an additive, not interactive, manner. In contrast, RO 15-1788 produced no changes when injected by itself in doses as high as 12 mg/kg and reversed chlordiazepoxide-induced but not ethanol-induced release of punished responding. RO 15-1788 also reversed the decrease in punished responding produced by FG 7142. Results suggest that ethanol does not interact directly with the benzodiazepine binding sites on the GABA/benzodiazepine ionophore complex to produce its anxiolytic action.Type of Medium: Electronic ResourceURL: -
14Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Arginine vasopressin ; EEG ; Spectral analysis ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Several studies have suggested that arginine vasopressin (AVP) may act centrally as a neurohormone or neuromodulator to produce electrophysiological and behavioral effects. However, there are few reports of EEG effects of AVP in unanesthetized, behaving animals. In the present study the EEG effects of “behaviorally relevant” subcutaneous (SC) doses of AVP (6 μg/kg) known to raise blood pressure were compared to “behaviorally relevant” intracerebroventricular (ICV) doses (0.1–1.0 ng) and multiple “toxic” ICV doses (1.0 μg) of AVP. Central injections of toxic doses of AVP produced behavioral arrest, bodily barrel rolling, and EEG slowing, but did not induce electrographic signs of seizure activity. Comparison of the spectral characteristics of the EEG revealed some similarities in the distribution of power between SC and the 1.0 ng ICV dose; whereas ICV doses of 0.1 and 0.5 ng produced power distributions that were different from those seen following saline or SC doses of AVP. The similarities in EEG activity between SC injections and the 1.0 ng ICV dose suggest a common brain state may be induced by the two routes of administration in those dose ranges.Type of Medium: Electronic ResourceURL: -
15Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Apomorphine ; Cis-[Z]-flupenthixol ; Dopamine ; Supersensitivity ; 6-Hydroxydopamine ; Cholecystokinin ; Haloperidol ; Nucleus accumbensSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Postsynaptic dopamine-cholecystokinin (CCK) interactions in the nucleus accumbens were studied in two behavioral preparations of DA receptor supersensitivity: chronic-neuroleptic treated and 6-hydroxydopamine (6-OHDA) denervated rats. Subcutaneous (SC) injections of apomorphine (APO; 0.15 mg/kg) in experiment 1 produced marked hyperlocomotion in rats following 12 days of pretreatment with cis-[Z]-flupenthixol (2 mg/kg; twice per day). Bilateral intra-accumbens (N.Acc.) microinjections of CCK-8 (2 ng and 2 μg) reliably reduced APO-stimulated hyperlocomotion. An intermediate CCK dose (20 ng) was without effect. No change in APO responsivity following chronic vehicle treatment was observed and the baseline APO response was not altered by CCK at any dose. Denervation of mesolimbic dopamine (DA) terminals by intra-N.Acc. injections of 6-hydroxydopamine (6-OHDA; 8 μg/side) in experiment 2 similarly resulted in intense locomotor hyperactivity after APO stimulation (0.1 mg/kg; SC). Bilateral intra-N.Acc. injections of CCK-8 (1, 10, 100 ng, and 1 μg) significantly attenuated the supersensitive locomotor response to APO. As in experiment 1, CCK produced “biphasic” dose-response effects with strong attenuation that persisted throughout the entire 60-min test at both high (1 μg) and low (1 ng) doses. Intermediate CCK doses (10 and 100 ng) produced only shortterm reductions in activity. Hypomotility induced by APO in SHAM-lesioned rats was not effectively reversed by CCK treatments. CCK had no effect on unstimulated baseline locomotor activity in either 6-OHDA or SHAM-lesioned rats. These results provide further evidence that CCK-8 modulates mesolimbic DA activity by functionally opposing the postsynaptic effects of DA in the region of the nucleus accumbens.Type of Medium: Electronic ResourceURL: -
16Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Morphine ; Opiates ; Dependence ; Nucleus accumbens ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that “euphoria” and “dysphoria” induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens.Type of Medium: Electronic ResourceURL: -
17Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Place-preference ; Amphetamine ; Locomotor behavior ; Conditioned locomotion ; Hyperactivity ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract The relationship between the motor-activating and positive-reinforcing properties of d-amphetamine was examined in the place-preference paradigm. Two groups of animals were trained to associate one environment with amphetamine, and another environment with saline. Annimals that were allowed to locomote in both environments during training later demonstrated a preference for the amphetamine-paired environment; animals in which hyperactivity was limited in both environments later failed to show any preference. However, both groups of animals demonstrated a conditioned locomotor activation to the amphetamine-associated environments. Our results suggest that a place-preference demonstrated for an amphetamine-paired environment depends on the ability of the drug to increase locomotor behavior.Type of Medium: Electronic ResourceURL: -
18Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Place preference ; Heroin ; β-endorphin ; Naloxone ; Reward ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract The role of β-endorphin as a possible mediator in the reinforcing properties of opiates was investigated using a conditioned place preference paradigm. Heroin, a synthetic opiate known to have reinforcing properties, produced a strong preference for an environment previously paired with heroin injection at all doses tested (0.25, 0.5, 1.0, 2.0 mg/kg SC). No such place preference was observed following saline injections. Rats also showed dose-dependent place preference for the environment paired with β-endorphin when injected intracerebroventricularly (significant dose was 2.5 μg). At higher doses (5.0 and 10.0 μg) rats showed no preference for the paired environment, but were catatonic. Pretreatment with naloxone (0.04, 0.2, 1.0 mg/kg SC) attenuated the rewarding effect of β-endorphin (2.5 μg) at all doses tested. The lowest dose of naloxone which had no aversive effect when tested alone could also significantly block the positive effect of β-endorphin. The reinforcing dose of β-endorphin (2.5 μg) also produced an increase in locomotor activity, when tested in photocell cages. This suggests that the hyperactivity induced by β-endorphin may contribute to the preference for an environment previously paired with the same drug. The reinforcing effect of β-endorphin is most probably mediated by the mu and/or delta opioid subtype receptor, since β-endorphin has a high affinity for these receptors. These results demonstrate positive reinforcing properties of β-endorphin in the central nervous system.Type of Medium: Electronic ResourceURL: -
19Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Memory ; Neuropeptides ; Vasopressin ; Oxytocin ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Adult male rats spend a great amount of time investigating novel juveniles. In contrast, rats re-exposed to the same juvenile 30 min after the initial exposure display little investigatory behavior. If the re-exposure occurs 2 h later, the juvenile is thoroughly investigated. These results have been interpreted to mean that rats form a transient memory for a particular juvenile. In the present study, memory was enhanced when the initial exposure to the juvenile was followed by another exposure to the same juvenile (retroactive facilitation) and impaired when exposure to the original juvenile was followed by exposure to another juvenile (retroactive interference). Arginine vasopressin had retroactive facilitating effects on social memory and these effects were blocked by the vasopressor antagonist dPTyr(Me)AVP. Moreover, the antagonist had retroactive interfering effects, since it impaired the recognition of a familiar juvenile. Oxytocin shared the same inhibitory pattern of action. These results suggest that neurohypophyseal peptides may have a prepotent role in modulating the mnemonic processing of chemosensory information associated with social interactions.Type of Medium: Electronic ResourceURL: -
20Articles: DFG German National LicensesStaff View
ISSN: 1432-2072Keywords: Key words Opiate ; Withdrawal ; Place aversion ; RatSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Rationale: Administration of low doses of opiate antagonists to morphine-dependent rats produces an aversive response as measured by a conditioned place aversion, but the time course of such a learned aversion is largely unknown. Objectives: The purpose of this experiment was to examine the time course for the expression of a place aversion to opiate withdrawal. Methods: Morphine-dependent rats were tested in a three-chamber place- aversion apparatus. The conditioning phase consisted of three pairings of either naloxone (15 µg/kg s.c.) or vehicle with two compartments, with the most similar time allotments during the preconditioning test. During the testing phase, rats were again allowed to explore the entire apparatus. Different groups were tested at 24 h, 1 week, 2 weeks, 4 weeks, 8 weeks, and 16 weeks post-conditioning (morphine-free tests). Results: A robust place aversion was recorded at every time point tested, including at 16 weeks. In previously published work, placebo-pelleted rats tested with naloxone at the same dose failed to show a place aversion and nondependent rats showed a stable lack of aversion at tests up to 56 days. Dependent animals without naloxone also failed to show a place aversion at any of those time points. Conclusions: In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.Type of Medium: Electronic ResourceURL: