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At least 1,171 records · Page 65Linked to original sources
PubMed2004

Mitochondrial electron transport as a source for nitric oxide in the unicellular green alga Chlorella sorokiniana.

Wild type (WT), and nitrate reductase (NR)- and nitrite-reductase (NiR)-deficient cells of Chlorella sorokiniana were used to characterize nitric oxide (NO) emission. The NO emission from nitrate-grown WT cells was very low in air, increased slightly after addition of nitrite (200 microM), but strongly under anoxia. Importantly, even completely NR-free mutants, as well as cells grown on tungstate, emitted NO when fed with nitrite under anoxia. Therefore, this NO production from nitrite was independent of NR and other molybdenum cofactor enzymes. Cyanide and inhibitors of mitochondrial complex III, myxothiazol or antimycin A, but not salicylhydroxamic acid (inhibitor of alternative oxidase) inhibited NO production by NR-free cells. In contrast, NiR-deficient cells growing on nitrate accumulated nitrite and emitted NO at very high equal rates in air and anoxia. This NO emission was 50% inhibited by salicylhydroxamic acid, indicating that in these cells the alternative oxidase pathway had been induced and reduced nitrite to NO.

Antimycin A↗
PubMed2004

Identification of prokaryotic homologues indicates an endosymbiotic origin for the alternative oxidases of mitochondria (AOX) and chloroplasts (PTOX).

The alternative oxidase is a ubiquinol oxidase that has been found to date in the mitochondrial respiratory chain of plants, some fungi and protists. Because of its sparse distribution among eukaryotic lineages and because of its diversity in regulatory mechanisms, the origin of AOX has been a mystery, particularly since no prokaryotic homologues have previously been identified. Here we report the identification of a gene encoding a clear homologue of the mitochondrial alternative oxidase in an alpha-proteobacterium, and the identification of three cyanobacterial genes that encode clear homologues of the plastid-specific alternative oxidase of plants and algae. These findings suggest that the eukaryotic nuclear genes for the alternative oxidases of mitochondria and chloroplasts were acquired via endosymbiotic gene transfer from the eubacterial ancestors of these two organelles, respectively.

Alphaproteobacteria↗
PubMed2004

Evidence for mitochondrial-derived alternative oxidase in the apicomplexan parasite Cryptosporidium parvum: a potential anti-microbial agent target.

The observation that Plasmodium falciparum possesses cyanide insensitive respiration that can be inhibited by salicylhydroxamic acid (SHAM) and propyl gallate is consistent with the presence of an alternative oxidase (AOX). However, the completion and annotation of the P. falciparum genome project did not identify any protein with convincing similarity to the previously described AOXs from plants, fungi or protozoa. We undertook a survey of the available apicomplexan genome projects in an attempt to address this anomaly. Putative AOX sequences were identified and sequenced from both type 1 and 2 strains of Cryptosporidium parvum. The gene encodes a polypeptide of 336 amino acids and has a predicted N-terminal transit sequence similar to that found in proteins targeted to the mitochondria of other species. The potential of AOX as a target for new anti-microbial agents for C. parvum is evident by the ability of SHAM and 8-hydroxyquinoline to inhibit in vitro growth of C. parvum. In spite of the lack of a good candidate for AOX in either the P. falciparum or Toxoplasma gondii genome projects, SHAM and 8-hydroxyquinoline were found to inhibit the growth of these parasites. Phylogenetic analysis suggests that AOX and the related protein immutans are derived from gene transfers from the mitochondrial endosymbiont and the chloroplast endosymbiont, respectively. These data are consistent with the functional localisation studies conducted thus far, which demonstrate mitochondrial localisation for some AOX and chloroplastidic localization for immutans. The presence of a mitochondrial compartment is further supported by the prediction of a mitochondrial targeting sequence at the N-terminus of the protein and MitoTracker staining of a subcellular compartment in trophozoite and meront stages. These results give insight into the evolution of AOX and demonstrate the potential of targeting the alternative pathway of respiration in apicomplexans.

Amino Acid Sequence↗
PubMed2006

Evaluation of rapidly disintegrating tablets containing glycine and carboxymethylcellulose.

A rapidly disintegration tablet in the oral cavity was prepared using a glycine as a disintegrant. Effect of disintegrant on the disintegration behavior of the tablet in the oral cavity was evaluated. Wetting time prepared from carboxymethylcellulose (NS-300) having the hardness of 4 kg was 3 s. Tablet containing NS-300 showed fastest disintegration compared to other formulations. These results suggested that NS-300 possessed excellent wetting nature and resulted in the rapid disintegration of tablet. Ethenzamide and ascorbic acid were added to the formulation, and their disintegration behavior were evaluated. Ethenzamide did not affect the disintegration property, however, ascorbic acid prolonged disintegration time. It was suggested that the tablet formulation containing NS-300 and glycine was highly applicable to water-insoluble drug, such as ethenzamide.

Ascorbic Acid↗
PubMed2006

Dissolution characteristics of cylindrical particles and tablets.

In this paper, dissolution characteristics of primary-particles and compressed tablets were investigated by experiments using a mathematical model. For the primary-particle, it was found that the dissolution rate increased with a decrease in the particle size. Assuming that primary-particles of size distribution were of cylindrical shape and that the dissolution occurs from the total external surface, an extended Nernst-Noyes-Whitney equation fitted to the experimental data well. As the influences of particle size and shape on thickness of a diffusion-boundary film were found to be quite low, the dissolution rate was considered to be affected by the specific surface area dominantly. Furthermore, the same model was applied to a compressed tablet and fitted to the data well. Though the rate constant obtained were not affected by the properties of primary-particles forming the tablet, it was found to increase with the apparent voidage which occupies the inter-particle volume of tablet diluent among less soluble particles. Consequently, an increase in the apparent voidage is presumed to accelerate penetration of water into the internal voids of the tablet. Thus, the dissolution going, the effective surface area inside the tablet is considered to be extended.

Kinetics↗
PubMed2006

Batch grinding kinetics of Ethenzamide particles by fluidized-bed jet-milling.

Ethenzamide solids as a representative active pharmaceutical ingredient (API) were batch-ground by means of a fluidized-bed jet-mill which is a relatively new equipment and promising for production in the pharmaceutical field. Thus, the characteristic grinding mechanism was investigated. As a result, the variation of the residual ratio with grinding time after milling was expressed simply by a mathematical model using only the first Kapur function, and it was consistent with experimental data satisfactorily. As the shape of the function was much different from that of inorganic compound and peculiar to API, a cubic function with respect to particle diameter was defined newly and well fitted to the experimental data. The function was also found to be affected by the operating parameters as the grinding gas pressure, the charge weight of raw material and the linear velocity at the grinding nozzle. According to the assessments of the breakage and the selection functions derived from the first Kapur function, it was found that the grinding mechanism of Ethenzamide particles was related with particle attrition mainly.

Kinetics↗
PubMed2007

Extrastriatal D2 and striatal D2 receptors in depressive illness: pilot PET studies using [11C]FLB 457 and [11C]raclopride.

BACKGROUND: Reduced dopaminergic function may occur in depressive disorders. In this paper the results of two pilot studies examining different aspects of the dopamine system in depression are presented. First, the binding of [(11)C]FLB 457 to extrastriatal D(2) receptors was measured in a group of depressed patients. Second, the hypothesis that selective serotonin reuptake inhibiting (SSRI) antidepressants affect the striatal binding of [(11)C]raclopride was tested. METHODS: In the first study the binding of [(11)C]FLB 457 was compared between 7 people with depression and 7 healthy controls. In the second study the binding of [(11)C]raclopride to striatal D(2/3) receptors was compared between 8 people taking SSRI antidepressant medication and 8 healthy controls. RESULTS: There was no difference in the binding of [(11)C]FLB 457 between the two groups. [(11)C]raclopride binding was reduced in the dorsal striatum of people taking antidepressants suggesting either that D(2/3) expression was reduced, or that dopamine release was increased, compared to untreated controls. LIMITATIONS: The depressed patients were not severely depressed and were not matched for gender with controls. In the raclopride group the patients and controls were not matched by gender and were taking different SSRI antidepressants. CONCLUSION: We found no support for the hypothesis that dopamine D(2) receptor expression is altered in extrastriatal brain regions in depression. SSRI antidepressants were associated with reduced [(11)C]raclopride binding in the dorsal striatum supporting the hypothesis that therapeutic effects of such drugs may, in part, be due to changes in the dopamine system.

Adult↗
PubMed2005

Inter-conversion of 15-MC-5 to 12-MC-4 manganese metallacrowns: structure and bioactivity of metallacrowns hosting carboxylato complexes.

Interaction of manganese with salicylhydroxamic ligands (shi) in methanol, in the presence of pyridine, leads to the formation of a series of 15-membered metallacrown (MC) Mn(II)(L)2[15-MCMn(III)N(shi)-5](py)6 or 7, (L=formato, benzoate or alkanoato ligand, py=pyridine). In the absence of pyridine, the Mn(II)(L)2[12-MCMn(III)N(shi)-4](MeOH)6 metallacrown was isolated and structurally characterized. The crystal structure of {[Mn(II)(HCOO)2][(15-MCMn(III)N(shi)-5)(py)7]}.py.1.9CH3OH.H2O (1) contains a neutral 15-membered metallacrown ring consisting of five Mn(III) and five shi(-3) ligands. The 15-membered metallacrown ring is formed by the succession of five structural moieties of the type [Mn(III)-N-O]. The diverse in the configuration (planar or propeller) for the ring Mn(III) ions gives the metallacrown core a bending structure. The crystal structure of {[Mn(II)(C6H5COO)2][(12-MCMn(III)N(shi)-4)(CH3OH)6]}.2CH3OH (2) contains a neutral 12-membered metallacrown ring consisting of four Mn(III) and four shi(-3) ligands. The 12-membered metallacrown ring is formed by the same way of succession of four structural moieties of the type [Mn(III)-N-O], while the presence of a planar only configuration of shi ligands around ring Mn(III) ions gives to the metallacrown core a planar structure. The encapsulated Mn(II) is six and seven-coordinate for (1) and (2), respectively, and is bound to the hydroximate oxygen of the metallacrown core and two oxygen atoms from the carboxylate ligands. Antibacterial screening data showed that, among all the compounds tested, manganese metallacrowns are more active compared to the simple manganese herbicide or carboxylate complexes, with increased efficiency for [15-MCMn(III)N(shi)-5] compared to the analogous [12-MCMn(III)N(shi)-4].

Anti-Bacterial Agents↗
PubMed2005

The concomitant expression and availability of conventional and alternative, cyanide-insensitive, respiratory pathways in Candida albicans.

The opportunistic oral pathogen Candida albicans expresses a cyanide-insensitive alternative oxidase (AOX) upon exposure to respiratory inhibitors that act downstream from coenzyme Q, and upon ageing of cells. To investigate whether the conventional pathway is retained when the alternative pathway is induced, cells were grown in the presence of sodium cyanide, a reversible inhibitor of cytochrome oxidase. AOX expression was monitored by Western blotting and the presence of cytochromes associated with complexes III and IV of the conventional pathway was monitored by recording spectra between 500 and 650 nm at 77K. The activities of complexes III and IV were determined in polarographic and enzyme-kinetic experiments using specific respiratory substrates and inhibitors. Results indicated that complexes III and IV are constitutively expressed and are functional in cells expressing AOX. Furthermore, the enzymatic activities of complexes III and IV were similar in mitochondrial preparations from cells grown with or without cyanide. We next investigated whether both pathways are simultaneously available for electron transfer from the Q pool to molecular oxygen. Respiration was virtually completely inhibited by the combination of cyanide and salicyl hydroxamic acid (SHAM) or antimycin A and SHAM, but only partly inhibited by either of these inhibitors alone. This indicates that electrons can in principle flow either through the conventional or the alternative respiratory pathway. The availability of two electron pathways in C. albicans and the potential use of either pathway endows this pleomorphic fungus with another level at which it can rapidly adjust to altered environmental conditions.

Antimycin A↗
PubMed2005

The effect of over-expression of the alternative oxidase in the procyclic forms of Trypanosoma brucei.

Trypanosome alternative oxidase (TAO) is the cyanide-resistant but SHAM-sensitive terminal oxidase of the mitochondrial electron transport chain in African trypanosomes. The bloodstream forms of Trypanosoma brucei lack cytochromes and respire exclusively via TAO. On the other hand, the insect, or procyclic form possesses a fully developed cytochrome system, and down regulates TAO several folds by reducing the stability of the TAO transcript. We expressed an ectopic copy of TAO in the procyclic form from a tetracycline regulated stable expression vector, in which the TAO 3'-UTR was replaced by T. brucei aldolase 3'-UTR. The TAO transcript produced from the ectopic copy was stably accumulated in the procyclic form. Upon induction with doxycycline, TAO protein level was gradually increased about five-fold within 72 h. TAO over-expression did not show any effect on the growth of the parasite. The rate of respiration and the SHAM-sensitive respiratory pathway capacity was increased about two- and five-fold, respectively, and the cytochrome-mediated respiratory pathway capacity was reduced two- to three-folds within 5 days after induction of TAO. Doxycycline induced TAO+ cells preferentially utilized CN-resistant, SHAM-sensitive pathway of respiration, whereas, in the control cells 70-80% of total respiration was via the CN-sensitive pathway. Moreover, we have found that increased expression of TAO caused about two-fold down regulation of cytochrome oxidase subunit IV, and cytochrome c1 protein level and also caused a four-fold up-regulation of the expression of the surface coat protein, GPEET procyclin in the procyclic form. This suggests that the expression of two terminal oxidases and the coat protein is linked in T. brucei.

Animals↗
PubMed2005

Cocaine induction of ERK proteins in dorsal striatum of Fischer rats.

Cocaine is an addictive psychostimulant that induces fos and opioid gene expression by activating the dopamine receptors and the PKA pathways in dopamine D1 and a glutamate NMDA-dependent mechanisms in the striatum. In this study, we show that a single cocaine administration induces ERK phosphorylation in the caudate/putamen of Fischer rats. This increase in Phospho-ERK is diminished by pre-administration of SCH23390, or MK801 but not with pre-administration of eticlopride. Furthermore, this single cocaine administration does not alter the levels of phospho-CREB protein or CREB-DNA bindings in the caudate/putamen protein extracts but does increase phospho-Elk-1 protein levels in the same extracts.

Animals↗
PubMed2004

Differentiation of extrastriatal dopamine D2 receptor density and affinity in the human brain using PET.

Dopaminergic neurotransmission in extrastriatal regions may play a crucial role in the pathophysiology and treatment of neuropsychiatric disorders. The high-affinity radioligands [(11)C]FLB 457, [(123)I]epidepride, and [(18)F]fallypride are now used in clinical studies to measure these low-density receptor populations in vivo. However, a single determination of the regional binding potential (BP) does not differentiate receptor density (B(max)) from the apparent affinity (K(D)). In this positron emission tomography (PET) study, we measured extrastriatal dopamine D2 receptor density (B(max)) and apparent affinity (K(D)) in 10 healthy subjects using an in vivo saturation approach. Each subject participated in two to three PET measurements with different specific radioactivity of [(11)C]FLB 457. The commonly used simplified reference tissue model (SRTM) was used in a comparison of BP values with the B(max) values obtained from the saturation analysis. The calculated regional receptor density values were of the same magnitude (0.33-1.68 nM) and showed the same rank order as reported from postmortem studies, that is, in descending order thalamus, lateral temporal cortex, anterior cinguli, and frontal cortex. The affinity ranged from 0.27 to 0.43 nM, that is, approximately 10-20 times the value found in vitro (20 pM). The area under the cerebellar time activity curve (TAC) was slightly lower (11 +/- 8%, mean +/- SD, P = 0.004, n = 10) after injection of low as compared with high specific radioactivity, indicating sensitivity to the minute density of dopamine D2 receptors in the this region. The results of the present study support that dopamine D2 receptor density and affinity can be differentiated in low-density regions using a saturation approach. There was a significant (P < 0.001) correlation between the binding potential calculated with SRTM and the receptor density (B(max)), which supports the use of BP in clinical studies where differentiation of B(max) and K(D) is not required. In such studies, the mass of FLB 457 has to be less than 0.5 microg injected to avoid a mass effect of the radioligand itself.

Autoradiography↗
PubMed2006

A comparison of recent parametric neuroreceptor mapping approaches based on measurements with the high affinity PET radioligands [11C]FLB 457 and [11C]WAY 100635.

In positron emission tomography (PET) studies, the detailed mapping of neuroreceptor binding is a trade-off between parametric accuracy and spatial precision. Logan's graphical approach is a straightforward way to quickly obtain binding potential values at the voxel level but it has been shown to have a noise-dependent negative bias. More recently suggested approaches claim to improve parametric accuracy with retained spatial resolution. In the present study, we used PET measurements on regional D2 dopamine and 5-HT1A serotonin receptor binding in man to compare binding potential (BP) estimates of six different parametric imaging approaches to the traditional Logan ROI-based approach which was used as a "gold standard". The parametric imaging approaches included Logan's reference tissue graphical analysis (PILogan), its version recently modified by Varga and Szabo (PIVarga), two versions of the wavelet-based approach, Gunn's basis function method (BFM) and Gunn et al.'s recent compartmental theory-based approach employing basis pursuit strategy for kinetic modeling (called DEPICT). Applicability for practical purposes in basic and clinical research was also considered. The results indicate that the PILogan and PIVarga approaches fail to recover the correct values, the wavelet-based approaches overcome the noise susceptibility of the Logan fit with generally good recovery of BP values, and BFM and DEPICT seem to produce values with a bias dependent on receptor density. Further investigations on this bias and other phenomena revealed fundamental issues regarding the use of BFM and DEPICT on noisy voxel-wise data. In conclusion, the wavelet-based approaches seem to provide the most valid and reliable estimates across regions with a wide range of receptor densities. Furthermore, the results support the use of receptor parametric imaging in applied studies in basic or clinical research.

Algorithms↗
PubMed2006

Asymmetry in dopamine D(2/3) receptors of caudate nucleus is lost with age.

Molecular and functional imaging techniques reveal evidence for lateralization of human cerebral function. Based on animal data, we hypothesized that asymmetry in dopamine neurotransmission declines during normal aging. In order to test this hypothesis, we measured dopamine D2/3 receptor availability with [18F]desmethoxyfallypride-PET (DMFP) in putamen and caudate nucleus (NC) of 21 healthy, right-handed males (24-60 years; 35+/-10). For volumetric analysis, high-resolution T1-weighted MR-images were obtained in 18 of the PET-subjects in order to assess possible age-related decreases in NC and putamen volume. The calculated DMFP binding potentials (BP) showed a right-ward asymmetry in NC of young subjects that decreased with age (r = 0.577, p = 0.006; Pearson correlation; two-tailed). An age-independent analysis showed a right-ward asymmetry in NC of the whole subject group (left: 1.49+/-0.35; right: 1.65+/-0.43 [mean+/-S.D.]; p = 0.020). No such side lateralization or age-effects could be found in the putamen. Volumes tended to be asymmetric in the putamen (right: 4.85+/-0.56 cm3; left: 4.64+/-0.86 cm3 [mean+/-S.D.]; p = 0.063), but not in NC. The decline of putamen volume during aging was significant in the right putamen (r = -0.613; p = 0.007; Pearson correlation; two-tailed). There were no other significant correlations between striatal volumes and age or BP. Because ventral striatal dopamine neurotransmission is involved in cognitive processes, this loss of physiological asymmetry in NC dopamine transmission during aging might be involved in age-related declines of cognitive performance.

Adult↗
PubMed2004

Effects of dopamine indirect agonists and selective D1-like and D2-like agonists and antagonists on cocaine self-administration and food maintained responding in rats.

A procedure is described for comprehensive evaluation of the effects of acute drug pretreatments on the reinforcing effects of cocaine using the rat self-administration assay in combination with a novel control assay of liquid-food maintained responding. In sessions comprised of five 20-min components, either complete dose-effect functions for cocaine self-administration or complete concentration-effect functions for liquid-food maintained responding were evaluated. The schedule of reinforcement (FR 5 TO 20-s), drug pretreatment doses and time intervals (0-30 min), and duration of sessions (108 min) were identical for cocaine- and food-reinforced test sessions. Whereas acute pretreatment with indirect dopamine agonists (D-amphetamine, GBR 12909) and D2-like agonists (7-OH-DPAT, quinelorane) produced dose-dependent leftward shifts in dose-effect functions for cocaine self-administration, D1-like agonists (SKF 82958, R-6-Br-APB) and dopamine antagonists (D1-like, SCH 39166; D2-like, eticlopride) shifted dose-effect functions for cocaine downward and rightward, respectively. Interestingly, with the indirect dopamine agonists but not the D2-like agonists, increased responding maintained by low cocaine doses was paralleled by increased responding maintained by low food concentrations. Moreover, three of the four direct agonists were moderately selective (< or =5-fold more potent) in decreasing cocaine self-administration relative to food maintained responding. When data were analyzed according to alterations in total cocaine intake, all of the agonists uniformly decreased total cocaine intake, whereas both antagonists increased total cocaine intake. Overall, this procedure was sensitive to leftward, downward and rightward shifts in cocaine dose-effect functions and should be useful for evaluating the nature of pharmacological interactions between novel compounds and self-administered cocaine, as well as the potential for altering cocaine self-administration selectively with candidate treatments for cocaine abuse and dependence.

Animals↗
PubMed2005

Cocaine-induced modulation of long-term potentiation in the CA1 region of rat hippocampus.

In order to further characterize the actions of cocaine on synaptic activity in the hippocampus, recordings of field excitatory postsynaptic potentials in the CA1 region of the rat hippocampal slice preparation were used to monitor drug effects on long-term potentiation (LTP) evoked in response to stimulation of the Schaffer collateral pathway. Cocaine had dose-dependent, biphasic effects on the magnitude of LTP at these excitatory synapses in the stratum radiatum ranging from a significant enhancement of LTP at intermediate drug concentrations (5-10 microM), to an inhibition of LTP at a relatively high drug concentration (30 microM). The local anesthetic lidocaine had only inhibitory effects on the induction of LTP at all concentrations examined (10-75 microM), whereas the monoamine transporter antagonists, WIN 35348 (1 microM) or GBR 12935 (5 microM) significantly enhanced the magnitude of LTP. The D(2)-like dopamine receptor antagonist, eticlopride was effective in preventing this action of cocaine, whereas pretreatment with the D(1/5) antagonist, SCH 23390 was ineffective. These results suggest that endogenously released dopamine, in the presence of cocaine (5-10 microM), can act via D(2)-like receptors to significantly increase the magnitude of LTP in the CA1 region of the hippocampus.

Adrenergic beta-Antagonists↗
PubMed2006

Amphetamine depresses excitatory synaptic transmission at prefrontal cortical layer V synapses.

Dopamine modulates the function of glutamatergic synapses in prefrontal cortex, modifying synaptic strength and influencing synaptic plasticity. Here we have explored the ability of endogenous dopamine, present in slices containing the prefrontal cortex, to influence excitatory synaptic transmission. We found that 10 microM amphetamine, which releases and blocks the reuptake of dopamine from dopaminergic nerve terminals, significantly depressed excitatory field potentials recorded in layer V during stimulation of layer II/III. The depression was reversible, dose dependent and correlated with increased paired pulse facilitation, suggesting that amphetamine inhibits the presynaptic release of glutamate. Pharmacological dissection of this response showed that dopamine D1 receptors are likely to mediate the effects of endogenous dopamine on excitatory synaptic transmission, with little effect of alpha2 adrenergic receptors, serotonin receptors, or D2 dopamine receptors. The time to peak amphetamine effect was longer than expected based on diffusion, suggesting that to raise dopamine levels in brain slices amphetamine may need to be transported into the presynaptic terminals. These results provide evidence that D1/D5 receptors depress glutamate release at this cortical synapse, and suggest that amphetamine will have profound and persistent effects on PFC functioning in vivo. Dysregulation of this mechanism could contribute to the impairment in cognitive performance associated with abnormal PFC dopamine receptor activation.

Adrenergic alpha-Antagonists↗
PubMed2005

D1-like and D2 dopamine receptor antagonists administered into the shell subregion of the rat nucleus accumbens decrease cocaine, but not food, reinforcement.

Cocaine self-administration experiments were designed to assess the respective roles of D1-like and D2-like dopamine receptors in the ventral forebrain in cocaine reinforcement. D1-like or D2-like dopamine receptor antagonists were microinjected into the nucleus accumbens core, nucleus accumbens shell, neostriatum or lateral septum prior to sessions in which cocaine was self-administered under a progressive ratio schedule by rats. The results indicated that administration of a D1/5 (SCH-23390) or a D2/D3/D4 (eticlopride), but not a D3 (U99194A) or D4 (L-750,667), dopamine receptor antagonist into the core and shell of the nucleus accumbens decreased the reinforcing efficacy of cocaine. However, in control experiments intra-accumbal core administration of SCH-23390 or eticlopride decreased food self-administration, whereas administration of these drugs into the accumbens shell had no effect on food reinforcement. Neither SCH-23390 nor eticlopride influenced cocaine reinforcement when administered into the neostriatum or lateral septum. Collectively, these results indicate that D1-like and D2 dopamine receptors in the nucleus accumbens shell selectively modulate the reinforcing efficacy of cocaine, whereas D1-like and D2 dopamine receptors in the accumbens core have a more general influence on reinforced behaviors.

Animals↗