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N E Goeders

Publications and source records attributed to N E Goeders.

At least 37 records · Page 2Linked to original sources
PubMed1996

Differential neuroendocrine and behavioral responses to cocaine in Lewis and Fischer rats.

Lewis (LEW) and Fischer 344 (F344) rats differ in responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as in their behavioral responses to drugs of abuse. The present experiments were conducted to compare hypothalamic corticotropin-releasing factor (CRF), plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone (CS) responses to cocaine (0-60 mg/kg, i.p.) in LEW and F344 rats. Acute administration of cocaine resulted in decreases in CRF and dose-related increases in CS and ACTH with significant differences observed between the strains. Cocaine also increased plasma norepinephrine concentrations. Although the CS response was increased in the F344 compared to LEW rats, the percent change in the CS response was markedly enhanced in LEW rats. Plasma ACTH concentrations as well as the percentage of the control response were dramatically increased at the 40 mg/kg cocaine dose in the LEW compared to F344 rats. Since cocaine-induced changes in HPA axis activity may contribute to behavioral responses to cocaine, another experiment was performed to compare the locomotor responses to novelty and to acute cocaine between LEW and F344 rats. Strain differences were not observed in the locomotor response to novelty or to cocaine. These data indicate that strain differences exist in the neuroendocrine response to acute cocaine exposure.

Adrenal Cortex↗
PubMed1996

Role of corticosterone in intravenous cocaine self-administration in rats.

The role of corticosterone in cocaine reinforcement was investigated in rats exposed to either response-contingent electric footshock, noncontingent shock or no shock prior to the initiation of testing for intravenous cocaine self-administration. Although rats from the two shock groups were consistently more sensitive to cocaine, plasma corticosterone was always significantly higher in all rats that subsequently self-administered low doses of cocaine compared to the rats that did not, regardless of the treatment condition. In fact, plasma corticosterone was always greater than approximately 150 ng/ml for rats that self-administered low doses of cocaine, suggesting that this stress hormone must be increased above a critical threshold for stable low-dose cocaine self-administration to subsequently occur. Plasma corticosterone was also measured following exposure to cocaine and was significantly elevated in rats from all three treatment groups during cocaine self-administration, provided that doses of cocaine that would maintain responding were tested. When the dose would not maintain self-administration, plasma corticosterone was markedly lower, suggesting that at higher concentrations, the cocaine injections alone were sufficient to increase plasma corticosterone above a critical threshold, even for rats which had low precocaine levels of the hormone. These data suggest a significant role for corticosterone in both the acquisition and maintenance of cocaine reinforcement in rats.

Animals↗
PubMed1994

Non-contingent electric footshock facilitates the acquisition of intravenous cocaine self-administration in rats.

The experiments described below were designed to investigate whether contingent versus non-contingent electric footshock would affect the acquisition of intravenous cocaine self-administration in rats. During the first component of a multiple schedule, triads of rats were trained to respond under a discrete-trial, fixed-ratio 10 schedule of food reinforcement. Random footshock presentation (0.6 mA) for the first and second rats from each triad was yoked to food lever responding by the rats in the first group only, while the third group of rats was never shocked. When stable baselines of food-reinforced responding were obtained, all three rats from each triad were allowed to self-administer increasing doses of cocaine (0.031-0.5 mg/kg per infusion) during the second component. Rats from the second group, receiving non-contingent footshock presentation, self-administered cocaine (0.125 mg/kg per infusion) at higher rates and at one-half the dose which maintained responding in rats from the other two treatment groups. Plasma corticosterone, measured before the acquisition of cocaine self-administration, was highly correlated with drug intake at this concentration for all three groups of rats. These data demonstrate that non-contingent experimental stress facilities the acquisition of intravenous cocaine self-administration in rats.

Animals↗
PubMed1993

Effects of alprazolam on intravenous cocaine self-administration in rats.

The specificity of benzodiazepine pretreatment on the reinforcing efficacy of cocaine was investigated using a multiple schedule of cocaine and food presentation. Cocaine was available under a fixed-ratio 4 schedule of reinforcement during 1 h of the session, while food was delivered under a discrete-trial, fixed-ratio 10 schedule during the other. Following initial exposure to alprazolam, responding maintained by both cocaine and food was significantly reduced. However, tolerance quickly developed to the sedative effects of alprazolam on food-maintained responding, while no reduction in the effects of the drug on cocaine self-administration was observed. Alprazolam (0.5 to 4.0 mg/kg, IP) significantly reduced cocaine intake without affecting food-maintained responding following subsequent testing with the drug. These data suggest a potential specific effect (e.g., anxiolytic) of alprazolam in cocaine reinforcement.

Alprazolam↗
PubMed1993

Effects of intracerebroventricular and intrahypothalamic cocaine administration on adrenocortical secretion.

Cocaine (COC) has been described as exerting potent stimulatory effects on the hypothalamo-pituitary-adrenocortical (HPA) axis. In the present study, we investigated the acute and chronic effects of intracerebroventricular and intrahypothalamic injections of COC in rats. Twenty minutes following intracerebroventricular injection of COC (1-100 micrograms), dose-dependent increases in plasma corticosterone (CS) were observed, although the highest dose tested (100 micrograms) evoked a significantly smaller response than that following 50 micrograms. Prior stressing of the animals resulted in elevated plasma CS levels (315 +/- 16 ng/ml) and significantly decreased plasma CS concentrations following 50 micrograms COC (87.8 +/- 3.2%). Injections above the hypothalamic paraventricular nucleus (PVN), the site of corticotropin-releasing-factor-secreting neurons which regulate HPA activity, required relatively higher doses of COC in order to elicit increases in plasma CS; injections of 0.5 microgram had no effect, 1 microgram resulted in an increase to 168 +/- 68 ng/ml (p < 0.005), and 2.5 micrograms produced an increase to 146 +/- 29 ng/ml (p < 0.025). Post-PVN injections of COC, behind the posterior margin of the PVN in the vicinity of the ventral noradrenergic ascending bundle, also required a high dose (2.5 micrograms) in order to elicit a plasma CS response (208 +/- 19 ng/ml; p < 0.005), with no significant response seen following 0.5 microgram COC. No effects of specific neurotoxic lesions of the catecholaminergic or serotonergic innervation of the hypothalamus were observed upon adrenocortical responses to COC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1993

Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens.

Adult male rats were trained to intracranially self-administer cocaine (50-100 pmol/100 nl infusion) into the medial prefrontal cortex and to simultaneously deliver an infusion of vehicle (100 nl of artificial cerebrospinal fluid) to a littermate control. When stable base lines of responding were obtained, each rat was implanted with an indwelling jugular catheter for the administration of radioactive precursors for the biogenic amine neurotransmitters. When stable rates of responding were re-established, the animals were infused with the radiolabeled precursors at the beginning of the behavioral session and were sacrificed 60 or 90 min later. Discrete response-contingent infusions of cocaine into the medial prefrontal cortex resulted in decreases in the turnover of dopamine and serotonin and increases in norepinephrine utilization at the site of self-injection compared to vehicle-infused controls. In contrast, DA turnover was significantly increased in the ipsilateral nucleus accumbens of the self-administering rats. These data demonstrate that discrete response-contingent cocaine infusions into the medial prefrontal cortex activate DA innervations of the nucleus accumbens, likely through descending pathways affecting A10 dopaminergic cell bodies, suggesting that neuronal activity similar to that observed after i.v. self-administration is initiated with the ICSA of the drug.

3,4-Dihydroxyphenylacetic Acid↗
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↗