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N E Goeders

Publications and source records attributed to N E Goeders.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1986

Benzodiazepine receptor GABA ratios: regional differences in rat brain and modulation by adrenalectomy.

GABA ratios were measured in several brain regions in sham-operated, adrenalectomized and adrenalectomized dexamethasone-injected rats. In sham-operated animals, GABA ratios varied 2.5-fold among the regions. In adrenalectomized animals the GABA ratios were increased in the hypothalamus and striatum but decreased in the hippocampus. Dexamethasone injection into adrenalectomized animals reversed the increased GABA ratio in the striatum. These data indicate that glucocorticoids can modulate GABA ratios, possibly by affecting the availability of the individual receptors in the receptor complex.

Adrenal Glands↗
PubMed1986

Benzodiazepine receptors in rat brain are altered by adrenalectomy.

The effects of adrenalectomy on benzodiazepine receptors in discrete regions of rat brain were examined using [3H]flunitrazepam as binding ligand. The concentration of benzodiazepine receptors was significantly increased by 25, 50 and 71% in hippocampus, striatum and hypothalamus, respectively, after adrenalectomy. In contrast, adrenalectomy did not affect the concentration of benzodiazepine receptors in cerebral cortex, olfactory bulb and cerebellum. No significant differences in the apparent binding affinity (Kd) values were seen following adrenalectomy in any brain region examined. The adrenalectomy-induced increases in [3H]flunitrazepam binding sites were completely reversed by glucocorticoid replacement with dexamethasone. These results demonstrate that adrenalectomy is capable of selectively modulating benzodiazepine receptors in brain regions presumably involved with glucocorticoid negative feedback. The data further suggest additional mechanisms by which endogenous hypothalamic-pituitary-adrenocortical hormones may affect 'anxiety' levels.

Adrenal Glands↗
PubMed1986

Neuropharmacological assessment of cocaine self-administration into the medial prefrontal cortex.

Neuronal systems involved in the initiation of reinforcement following the response-contingent delivery of cocaine into the medial prefrontal cortex were investigated. Dose-effect analyses demonstrated that different concentrations of cocaine result in distinguishable patterns of self-administration which could be empirically determined by measuring the relative frequency distribution of the interinfusion intervals. The substitution of equimolar d-amphetamine or lidocaine resulted in rates and patterns of responding similar to vehicle or a low dose of cocaine, suggesting that reinforcement occurs from actions on specific receptors rather than through a local anesthetic neuronal blockade or through properties of a general psychomotor stimulant. The co-infusion of equimolar concentrations of sulpiride attenuated intake and produced patterns of responding similar to those seen after decreasing the cocaine dose consistent with an excitatory role for D2 dopaminergic receptors in these processes. Sulpiride and cocaine may act at separate sites since the decreased intake was not reversed by increasing the concentration of cocaine. D1 dopaminergic, muscarinic-cholinergic and beta-noradrenergic receptor antagonists either did not modulate drug-intake or had minimal effects. Cocaine reinforcement may result in part from an activation of D2 receptors initiating neuronal activity in pathways or circuits mediating reinforcement processes.

Amphetamine↗
PubMed1986

Reinforcing properties of cocaine in the medical prefrontal cortex: primary action on presynaptic dopaminergic terminals.

The presynaptic mechanisms involved in the initiation of cocaine reinforcement were investigated using neurotoxin lesions. Rats were trained to intracranially self-administer cocaine (50 to 90 pmol) into the medial prefrontal cortex and after dose-effect analyses were completed, each rat received a unilateral 6-hydroxydopamine lesion (4 micrograms in 0.2 microliter) at the self-administration site. The lesion selectively decreased dopamine content in the medial prefrontal cortex (-45%) and decreased cocaine-maintained responding to vehicle levels. Lever-pressing could be reinstated by substituting dopamine (300 pmol) but not serotonin for cocaine. Dopamine self-administration was attenuated by including equimolar concentrations of the D2 dopaminergic antagonist sulpiride in the injectate. These results suggest that the initiation of reinforcing neuronal activity in the medial prefrontal cortex appears to result in part through the direct interaction of cocaine with presynaptic reuptake sites associated with dopaminergic nerve endings. The resulting increased synaptic concentration of the neurotransmitter may then interact with postsynaptic D2 binding sites to activate neuronal systems involved in the mediation of this reinforcement.

Animals↗
PubMed1985

Benzodiazepine receptor binding in vivo with [3H]-Ro 15-1788.

In vivo benzodiazepine receptor binding has generally been studied by "ex vivo" techniques. In this investigation, we identify the conditions where [3H]-Ro 15-1788 labels benzodiazepine receptors by true "in vivo" binding, i.e. where workable specific to nonspecific ratios are obtained in intact tissues without homogenization or washing. [3H]-Flunitrazepam and [3H]-clonazepam did not exhibit useful in vivo receptor binding.

Animals↗
PubMed1985

Reinforcing stimulus properties of endocoids.

Intracranial self-administration methodologies can be used to directly assess the neurobiological substrates of the reinforcing stimulus properties of drugs and endogenous ligands that may bind to receptors initiating these neuronal events. The reinforcing properties of the intracranial infusion of methionine enkephalin into the nucleus accumbens where it is released from nerve endings were demonstrated. The mechanisms of the reinforcing stimulus resulting from the intracranial self-administration of cocaine into the medial prefrontal cortex were shown to require presynaptic dopaminergic intervations and postsynaptic dopaminergic D2 receptors. The endogenous ligand that competes for cocaine binding may initate a reinforcing stimulus through similar mechanisms which could be directly assessed with intracranial self-administration procedures.

Animals↗
PubMed1984

Reinforcer interactions under concurrent schedules of food, water, and intravenous morphine.

Responding by six rats was maintained under a concurrent chained fixed-ratio 1, fixed-ratio 9 schedule (conc chain FR1 FR9 ) of food, water, and morphine presentations. The subjects had continuous access to the schedule contingencies on a reversed 12-h light-dark cycle. Local rates and temporal patterns were very similar for responding maintained by the three reinforcers with food and water intake occurring predominantly during the dark cycle, while morphine infusions were evenly distributed. Food and water extinction (24-h duration) decreased the number of ratios completed on both the food and water levers. Moreover, food extinction resulted in a large increase in I.V. morphine self-administration. Morphine extinction increased responding on the morphine lever while almost eliminating responding on the water lever. Changes in the dose of morphine (2.5-40 mg/kg/injection) did not significantly affect food and water intake, but were inversely related to responding on the morphine lever. Saline substitutions resulted in effects similar to those observed during morphine extinction. The schedule used in this study provides a method for examining the specificity of a number of pharmacological and neurochemical manipulations.

Animals↗
PubMed1984

Self-administration of methionine enkephalin into the nucleus accumbens.

Microinfusions of the endogenous opiate neurohumor, methionine enkephalin, into the nucleus accumbens initiated a reinforcing stimulus in a dose-related manner. The reinforcing nature of this intracranial self-administration was evaluated with intermittent schedules of reinforcement and a two-lever discrimination procedure. Opiate receptors are likely responsible for the initiation of this reinforcing stimulus since naloxone effectively blocked self-administration. These data suggest the mediation of opiate reinforcement through interactions with opiate receptors in brain regions outside the ventral tegmental area, questioning the current dopamine hypothesis for the initiation of these reinforcement processes.

Animals↗