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N E Goeders

Publications and source records attributed to N E Goeders.

At least 19 recordsLinked to original sources
PubMed1992

Chronic cocaine enhances serotonin autoregulation and serotonin uptake binding.

Repeated cocaine intoxication can result in the development of behavioral sensitization in animals and psychosis in humans, phenomena that have been associated with alterations in dopamine (DA) function. Using electrophysiologic and autoradiographic techniques, modifications of central serotonin (5-hydroxytryptamine; 5-HT) systems were investigated in rats treated with a regimen of cocaine administration that produced behavioral sensitization. The inhibitory response of single 5-HT neurons in the dorsal raphe (DR) to (-)-cocaine, the 5-HT uptake inhibitor fluoxetine or the 5-HT1A agonist 8-hydroxy-2-[di-N-propylamino]tetralin (8-OHDPAT) was significantly enhanced in cocaine-treated rats. Furthermore, several brain areas that contain either cell bodies (DR) or terminals for 5-HT (medial and sulcal prefrontal cortex, frontal cortex) showed cocaine-induced elevations in [3H]imipramine-labeled 5-HT uptake sites, while [3H]-8-OHDPAT-labeled 5-HT1A receptors were decreased only in the central medial amygdala. These results suggest that modifications of autoregulatory mechanisms secondary to alterations of 5-HT uptake processes may contribute to the development of cocaine sensitization.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Anxiogenic effects of acute and chronic cocaine administration: neurochemical and behavioral studies.

The effects of cocaine on defensive withdrawal behavior in rats and elevated plus-maze behavior in mice were investigated. Cocaine (20 mg/kg IP) injected daily for 7 or 14 days induced defensive withdrawal; that is, the latency to emerge from a small chamber in an open field and the mean time in the chamber were both significantly increased. Acute cocaine administration also induced defensive withdrawal, and this effect was prevented by prior treatment with chlordiazepoxide (5 mg/kg IP). Both acute and chronic cocaine treatments significantly increased plasma concentrations of corticosterone and reduced the ratios of 3,4-dihydroxyphenylacetic acid to dopamine and 5-hydroxyindoleacetic acid to serotonin in several brain regions. Further evidence for an acute anxiogenic effect of cocaine was obtained from mice studied in the elevated plus-maze. Acute cocaine administration decreased both the number of entries into and the time spent in the open arms of the maze. These results taken together strongly support an anxiogenic action of acute and chronic cocaine administration.

Animals↗
PubMed1991

Cocaine differentially affects benzodiazepine receptors in discrete regions of the rat brain: persistence and potential mechanisms mediating these effects.

The effects of cocaine on benzodiazepine (BZD) receptor binding in the rat brain were investigated using homogenate receptor binding and quantitative autoradiography. Although acute cocaine injections produced little or no effect on BZD binding sites, chronic administration resulted in differential effects in brain regions associated with the mesocorticolimbic and nigro-striatal dopaminergic neuronal system, respectively. BZD receptor binding was increased significantly in the caudate nucleus and decreased in the substantia nigra for up to 2 days after the final injection, whereas binding was decreased in the nucleus accumbens and medial prefrontal cortex and increased in the ventral tegmental area after daily injections of cocaine for 15 days. Binding was altered significantly only in the medial prefrontal cortex and ventral tegmental area 2 weeks after the final cocaine injection. Intraventricular injections of 6-hydroxydopamine attenuated or reversed the cocaine-induced changes in BZD receptor binding, suggesting that these effects were mediated, in part, through the effects of the drug on dopaminergic neuronal activity. Dopamine may be involved in the regulation of BZD receptors because 6-hydroxydopamine administration produced changes in BZD receptor binding in saline-treated rats that were generally in the opposite direction to those observed in cocaine-treated rats following sham treatment.

Animals↗
PubMed1990

Chronic cocaine administration alters corticotropin-releasing factor receptors in the rat brain.

Two groups of 12 rats received daily injections of cocaine (20 mg/kg, i.p.) or saline for 15 days following bilateral infusions of 6-hydroxydopamine or vehicle into the lateral ventricles. Cocaine administration resulted in significant decreases in CRF receptor labeling primarily in brain areas associated with the mesolimbic/mesocortical dopaminergic system. All of the cocaine-induced changes in CRF binding were attenuated in the lesioned animals, suggesting that these effects may be mediated, in part, through the actions of the drug on dopaminergic neuronal activity. Dopamine may also be involved in the release of CRF in the rat brain since the purported loss of dopaminergic innervations resulted in increased CRF binding in the saline-treated animals.

Animals↗
PubMed1989

Punishment modifies the effects of chlordiazepoxide and benzodiazepine receptors.

Littermate groups of male albino rats responded under a procedure which generated comparable rates of punished and nonpunished responding. Chlordiazepoxide (3.0-30.0 mg/kg, IP) increased punished responding but had no effect on nonpunished responding. Homogenate receptor binding studies with [3H]Ro 15-1788 indicated increased benzodiazepine receptor binding in the striatum of rats who received shock. Moreover, a third group of rats exposed to noncontingent shock showed greater increases than those whose responses had been punished, suggesting that predictability and control of shock may have attenuated the effects of the noxious stimulus. Increased binding seen in the cerebellum, however, was related to the punishing effects of the electric shock since it occurred only in those animals receiving response-contingent shock. There were no changes in binding affinity in any of the brain regions tested. Site-specific alterations benzodiazepine receptors following electric footshock are related to the contingencies under which the noxious stimuli are administered. Furthermore, changes in benzodiazepine receptor binding may underlie the differential effects of benzodiazepine agonists on punished and nonpunished responding.

Animals↗
PubMed1989

Chlordiazepoxide alters intravenous cocaine self-administration in rats.

This investigation was designed to examine the effects of benzodiazepines on intravenous cocaine self-administration in rats. Pretreatment with low doses of the benzodiazepine receptor agonist, chlordiazepoxide (0.3 to 1.0 mg/kg, IP), resulted in small but nonsignificant increases in drug intake with 0.5 mg/kg cocaine, while higher doses (10 mg/kg, IP) significantly decreased drug intake in all rats tested. The effects of chlordiazepoxide on self-administration were attenuated when the concentration of cocaine was increased to 1.0 mg/kg, suggesting that chlordiazepoxide was opposing rather than augmenting the pharmacological actions of cocaine. Pretreatment with the benzodiazepine receptor antagonist, Ro 15-1788 (1.0 to 10 mg/kg, IP), had no effect on self-administration, suggesting that the reinforcing properties of cocaine do not result from direct interactions with benzodiazepine receptors. The result of this investigation demonstrate that chlordiazepoxide alters intravenous cocaine self-administration in rats. Although additional research will be necessary to confirm these data, the results of this investigation suggest that chlordiazepoxide may decrease the reinforcing efficacy of cocaine through indirect actions on dopaminergic neuronal activity potentially mediated through GABAergic mechanisms via benzodiazepine receptor activation.

Animals↗
PubMed1988

Buspirone enhances benzodiazepine receptor binding in vivo.

The effects of buspirone on benzodiazepine receptors labelled in vivo with [3H]Ro 15-1788 were investigated. While buspirone did not affect the binding of benzodiazepine receptors in vitro, significant dose-related increases were observed in the in vivo labelling of benzodiazepine receptors in mice. However, similar results were also obtained with various neuroleptic agents and apomorphine. Potential mechanisms that may account for these results are discussed, but the data suggest caution in the use of [11C]Ro 15-1788 in positron emission tomography scanning in humans, since labelling by Ro 15-1788 may be affected by factors unrelated to direct changes at the benzodiazepine receptor site.

Animals↗
PubMed1988

Lack of an effect of 6-hydroxydopamine lesions of the nucleus accumbens on intravenous morphine self-administration.

The neurotoxin, 6-hydroxydopamine (6-OHDA), has been used to selectively destroy dopamine containing neurons in discrete brain regions. Lesions of the nucleus accumbens with this neurotoxin decrease or eliminate cocaine and amphetamine self-administration and either increase or do not affect opiate self-administration in rats with unrestricted access to food and water. This study reports the effects of 6-OHDA lesions of the nucleus accumbens on responding maintained by food, water or morphine (3.3 mg/infusion). Six male rats with continuous access to three response levers were trained on a concurrent chained, fixed-ratio 1, fixed-ratio 9 schedule of reinforcer presentation. After stable patterns of responding were maintained by the three reinforcers, dose-effect curves for morphine were determined by substituting other doses of morphine or vehicle for 24-hour periods. Bilateral sham vehicle or 6-OHDA lesions of the nucleus accumbens were then completed and the effects of the lesion on food, water and morphine intake determined. Dose-effect evaluations were repeated after the lesion. The 6-OHDA lesions did not significantly affect responding maintained by food, water or morphine. The absence of an effect is most likely not the result of an insensitive baseline since other neurotoxin lesions produce long-term and selective decrements in morphine self-administration without affecting food and water responding. Like so many other manipulations, the magnitude of the effect that a neurotoxin lesion can exert on behavior may depend on the specific procedures that are used to maintain responding.

Animals↗
PubMed1988

Kainic acid lesions of the nucleus accumbens selectively attenuate morphine self-administration.

The influence of kainic acid lesions of intrinsic and efferent neurons of the central medial nucleus accumbens on responding simultaneously maintained by food, water and morphine self-administration was assessed. Rats were trained on a multioperant baseline to respond on three different levers that resulted in either a food pellet, the presentation of a water dipper or an infusion of morphine. While responding on the morphine lever was related to dose (0.83-13.2 mg/infusion), increasing concentrations of the drug had little or no effect on responding maintained by food and water before the lesion. Bilateral infusions of the neurotoxin into the nucleus accumbens decreased morphine self-administration but did not appreciably alter food or water intake. Food extinction probes before the lesion produced significant increases in drug intake and decreases in responding on the water lever, but the neurotoxin lesion attenuated the food extinction induced decrease in water intake. These data suggested that kainic acid lesions of the nucleus accumbens decrease the reinforcing efficacy of morphine but do not alter the reinforcing properties of food and water. The neuronal systems potentially involved in mediating the reinforcing effects of environmental events are discussed.

Animals↗
PubMed1987

Effects of 5,7-dihydroxytryptamine lesions of the nucleus accumbens on rat intravenous morphine self-administration.

The role of serotonergic innervations of the nucleus accumbens in the processes maintaining intravenous morphine self-administration were assessed. Pairs of male rat littermates were implanted with intravenous jugular catheters and bilateral injection guide cannulae into the central medial nucleus accumbens, made physically dependent on morphine and then allowed to intravenously self-administer with continuous access. When stable baselines of drug intake were obtained (2-3 weeks), one of each pair received bilateral microinjections of vehicle and the other 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus accumbens. Response independent infusions of morphine were delivered for 24 hours at the previous rate of self-injection and the animals were again allowed to self-administer while drug intake was monitored for thirteen days. The littermate pairs were then sacrificed by immersion in liquid nitrogen, the brains removed at -20 degrees C and frozen sections of the cannulae tract taken for histological assessment. The nucleus accumbens, anterior caudate nucleus and pyriform cortex were removed at -20 degrees C and biogenic monoamine content determined. The 5,7-DHT lesions resulted in a significant increase in drug intake and significantly decreased the content of serotonin (5-HT) and 5-hydroxyindoleacetic acid in the nucleus accumbens (-49% and -30%, respectively) and 5-HT in the anterior caudate nucleus (-14%) and pyriform cortex (-17%). Dose-effect relationships were assessed in four additional animals before and after similar bilateral 5,7-DHT lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1987

Intracranial self-administration methodologies.

Intracranial drug self-administration (ICSA) offers a relatively new approach for investigating the neurobiological mechanisms involved in brain reinforcement processes. Discrete brain regions responsible for the initiation of neuronal activity associated with the response-contingent delivery of a drug reinforcer can be identified using these procedures since the drug is infused directly into a specific brain locus. In the last decade, several papers have appeared in the literature reporting the self-administration of various substances into a number of brain regions. However, different laboratories often employ diverse methodological procedures to demonstrate ICSA, and this can lead to erroneous conclusions when comparing data from different investigations. This review presents a critical evaluation of the current status of research in this area and suggests behavioral as well as methodological guidelines for future investigations to follow.

Animals↗
PubMed1987

Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens.

A variety of clinical and animal data suggest that the repeated administration of cocaine and related psychomotor stimulants may be associated with a behavioral sensitization whereby the same dose of the drug results in increasing behavioral pathology. This investigation was designed to determine the effects of chronic cocaine administration on the binding of [3H]sulpiride, a relatively specific ligand for D2 dopaminergic receptors, in the rat brain using in vitro homogenate binding and light microscopic quantitative autoradiographic methodologies. Chronic daily injections of cocaine (10 mg/kg, i.p.) for 15 days resulted in a significant decrease in the maximum concentration of sulpiride binding sites in the striatum and a significant increase in the maximum number of these binding sites in the nucleus accumbens. No significant differences in binding affinity were observed in either brain region. These data suggest that chronic cocaine administration may result in differential effects on D2 receptors in the nigro-striatal and mesolimbic dopaminergic systems.

Animals↗