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D C Roberts

Publications and source records attributed to D C Roberts.

At least 127 records · Page 7Linked to original sources
PubMed1984

Destruction of the locus coeruleus or the dorsal NE bundle does not alter the release of punished responding by ethanol and chlordiazepoxide.

The hypothetical involvement of central noradrenergic projections in the manifestation of "anxiety" and the "anti-anxiety" effects of alcohol and benzodiazepines was tested in an operant conflict situation by examining the effects of destruction of this noradrenergic system on response rates. Rats were trained on a Geller-Seifter conflict test [9] modified for incremental shock [21], in which two food-reinforced lever press components were separated by a time-out. Responses during the "food-alone" component (RI) were reinforced on a random interval schedule-30 sec; responses during the "time-out" component were never reinforced; and responses during the conflict component (CONFLICT) were continuously reinforced with both food and shock. This shock strength increased incrementally with each successive shock during the conflict period. Each session consisted of two cycles of a 5 min RI period, a two min time out, and a two min CONFLICT period presented in succession. Both ethanol (0.5 to 1.0 g/kg) and chlordiazepoxide (5 and 10 mg/kg) produced a significant increase in punished responding during the CONFLICT component. Ethanol, but not chlordiazepoxide (CDP) also significantly decreased responding during the RI component. Virtual total destruction of the dorsal noradrenergic projection with 6-hydroxydopamine (6-OHDA), or destruction of the locus coeruleus itself, failed to significantly alter baseline responding or the release of punished responding to ethanol or CDP. These results do not support the hypothesis that the locus coeruleus projections have an essential role in "anxiety" or in the "anxiety-reducing" properties of ethanol or the benzodiazepines.

Animals↗
PubMed1984

Deficits in conditioned avoidance responding following adrenalectomy and central norepinephrine depletion are dependent on postsurgical recovery period and phase of the diurnal cycle.

Rats that had undergone combined dorsal noradrenergic bundle lesion (DNBL) and bilateral adrenalectomy were impaired in acquiring a conditioned avoidance response when tested 1 week following surgery. Normal acquisition was observed, however, when testing occurred 3 weeks or more after surgery despite low levels of both plasma corticosterone and brain norepinephrine at that time. Furthermore, neither neonatal systemic administration of 6-hydroxy-dopamine to deplete forebrain norepinephrine, combined with the corticosterone inhibitor metyrapone, nor the pharmacological blockade of noradrenergic receptors, combined with adrenalectomy, disrupted acquisition of the avoidance response. Thus, the combination of forebrain norepinephrine loss and low plasma corticosterone does not inevitably impair avoidance acquisition. Rather, the determining factor for such impairment seems to be the interval between surgery and testing. The impairment at 1 week following DNBL and adrenalectomy occurred only for rats tested during the dark phase of their light cycle. In addition, the DNBL abolished the effect of the light/dark cycle on posttraining plasma corticosterone. These results demonstrate the importance of the phase of the rat's diurnal rhythm on both the hormonal and the behavioral effects of altering the pituitary-adrenal axis and/or forebrain norepinephrine. Because adrenocorticotropin, corticosterone, and vasopressin all show diurnal patterns of release, it cannot be determined at this time which, if any, of these hormones is most important for the behavioral results reported here.

Adrenal Cortex Hormones↗
PubMed1983

Failure to replicate the dorsal bundle extinction effect: telencephalic norepinephrine depletion does not reliably increase resistance to extinction but does augment gustatory neophobia.

Depletion of telencephalic noradrenaline (Ne), caused by lesion of the dorsal tegmental bundle, has been reported to increase persistence of non-reinforced responding in various operant tasks. This has been referred to as the dorsal bundle extinction effect (DBEE). In an effort to reproduce this effect, rats receiving 6-hydroxydopamine lesions of the dorsal Ne bundle (DB-6-OHDA) were compared to controls during extinction of a continuous food rewarded (CRF) lever-press response. While the lesion group showed an increase in responding during initial extinction, no significant difference in resistance to extinction using a 2-min non-response criterion was obtained. Moreover, no differences in reinforced response rates were observed with CRF, fixed ratio (FR-15, FR-30, FR-60) or variable interval (VI-30, VI-60, VI-120 s) schedules of reinforcement. In order to test the hypothesis that the DBEE is dependent on time of behavioral testing after surgery, subsequent experiments were performed where rats began CRF operant training 5, 17, 31 or 110 days post-lesion. No differences in resistance to extinction were observed between lesion and control rats at any post-lesion interval. Neonatal treatment with 6-OHDA which permanently lesions forebrain Ne terminals also failed to prolong extinction. Finally, when both DB-6-OHDA and neonatal rats were given a choice between water and saccharin the lesioned animals exhibited a neophobic reaction whereby they drank significantly less saccharin. We conclude that while the DBEE is not a reliably reproducible phenomenon other effects of forebrain Ne lesions, such as neophobia, appear to be robust.

Afferent Pathways↗
PubMed1983

Long-term reduction in beta-adrenergic receptor binding after amygdala kindling in rats.

The long-term effect of amygdala kindling on beta-adrenergic receptor binding was examined in three groups of Wistar rats. The animals in one of two kindled groups received six stage-5 generalized convulsions, one each day, and then were not stimulated for 23 days before being killed (23-day group). Animals in the other kindled group received only five generalized convulsions prior to 22 days of no stimulation but then received their sixth convulsion 1 day before being killed (1-day group). All animals including the operated controls experienced similar handling. A significant reduction in [3H]dihydroalprenolol binding in the anterior cortex and kindled amygdala was observed in the 23-day animals compared with control animals, whereas the 1-day animals exhibited intermediate values which were not different from either of the other two groups. Thus, amygdala kindling results in a long-lasting reduction in beta-adrenergic binding which, paradoxically, can be partially ameliorated by a single convulsion 1 day before killing.

Amygdala↗
PubMed1983

Effects of amphetamine and apomorphine on locomotor activity after 6-OHDA and electrolytic lesions of the nucleus accumbens septi.

Spontaneous locomotor activity was markedly elevated by electrolytic lesions of the nucleus accumbens. This was true whether or not the dopaminergic input to this nucleus was previously destroyed by injection of 6-hydroxydopamine (6-OHDA) into the region. In animals with electrolytic lesions the locomotor stimulant action of d-amphetamine sulfate (1.5 mg/kg SC) was occluded, while a moderately low dose of apomorphine (0.25 mg/kg SC) produced a striking decrease of locomotor activity. The results are consistent with the view that the efferents of neurons in the nucleus accumbens exert an inhibitory influence on locomotor activity. Hyperactivity results when these efferents are destroyed. The results are also consistent with the view that the locomotor depressant action of apomorphine is mediated, at least partly, by an action at a site other than the nucleus accumbens.

Animals↗
PubMed1983

Application of pattern recognition techniques to the analysis of protein crystal structure data. I. Characteristics of per-residue side chain contact frequency distributions.

A statistical study of amino acid side chain contact interactions was carried out using a data set based on 36 protein structures. For each type of amino acid, a distribution of per-residue inter-side-chain contacts was obtained, over the observed span of zero to 11 contacts per residue. Significant observations included the following: 1) The mean number of inter-side-chain contacts is proportional to side chain surface area with the exception of Lys and Arg. 2) The mean number of contacts was greater for amino acids in beta-sheet relative to alpha-helical regions. 3) The more polar or surface-loving amino acids exhibited non-normal distributions, whereas distributions for the non-polar or interior-loving amino acids fell within accepted limits of normality.

Amino Acids↗
PubMed1983

Estimation of peptide hormone noncovalent binding site functionality from frequencies of interaction of amino acid side chains in proteins.

A method is described for estimating the amino acid side chain functional groups most likely to occur at a receptor site (or other protein-type binding site) given a particular peptide hormone sequence. The predictions are based on mutual affinities of amino acid side chains, as manifested in the frequencies of side chain contacts occurring in proteins. The relative merits of various measures of these affinities are discussed, and a new set of contact frequency data based on 36 proteins (coordinate data taken from the Brookhaven Protein Data Bank) is presented. Evaluation of predictions was carried out using subunit-subunit interfaces as models for peptide-receptor association; accuracy of guesses was found to be 3-4 times better than random, according to this measure. Computer programs for carrying out all requisite data manipulations are described.

Amino Acids↗
PubMed1983

Effects of d-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens.

After training under a fixed-interval 60 sec schedule of food presentation in the presence of a water tube (to permit schedule-induced licking), groups of rats received either 6-hydroxy-dopamine (6-OHDA)(8 micrograms base/2 microliters) or 0.2% ascorbate-0.9% saline vehicle bilaterally into the nucleus accumbens. 6-OHDA produced greater than 80% depletion of the catecholamines dopamine and norepinephrine and the dopamine metabolite dihydroxyphenylacetic acid in the nucleus accumbens and olfactory tubercle, but nonsignificant depletions in the corpus striatum. The behavior of the groups treated with 6-OHDA ("lesion") and vehicle ("sham") was assessed for up to 58 days postoperatively. In the first few days after 6-OHDA, the lesion group showed reductions in high rates of responding toward the end and in high rates of licking at the beginning of the fixed-interval. However, licking was increased during later portions of the fixed interval in the lesion group. d-Amphetamine (0.25-2.0 mg/kg) increased low rates but decreased high rates of schedule-controlled responding, while generally reducing licking. The lesion group showed attenuated rate-reducing effects of d-amphetamine. In contrast, the lesion group showed enhanced rate-reducing effects of apomorphine (0.025-0.1 mg/kg) on both schedule-controlled responding and schedule-induced licking. In a second determination of the effect of d-amphetamine (0.25-2.0 mg/kg), schedule-induced locomotor activity was recorded and the water tube was removed. The lesion group showed attenuated rate-increasing and rate-decreasing effects of d-amphetamine upon schedule-controlled responding and reductions in the drug-induced increases in locomotor activity. The results are discussed in terms of the functions of dopamine in the control of behavior and in the mediation of the response to d-amphetamine and apomorphine.

Animals↗
PubMed1982

Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats.

6-Hydroxydopamine-induced destruction of dopaminergic terminals in the nucleus accumbens have been shown previously to disrupt cocaine and amphetamine self-administration. We sought to determine whether lesions of the DA cell bodies in the ventral tegmental area (VTA) which give rise to the DA innervation of the n. accumbens, would also disrupt cocaine self-administration behavior. Rats were trained to self-inject cocaine (0.75 mg/kg) for 4 hr/day. After a stable baseline was established, one group of rats received bilateral injections of 6-OHDA (4 micrograms/l microliter) into the VTA. Control rats received vehicle injections. When retested on the fifth day post-lesion, all of the 6-OHDA treated animals showed a long lasting reduction in cocaine intake. Three animals did not reinitiate cocaine self-administration after the lesion, although each showed stable post-lesion responding for apomorphine. The surgery had no effect on cocaine self-administration in control animals. These data support the hypothesis that dopaminergic mechanisms are necessary for the normal expression of cocaine self-administration.

Animals↗
PubMed1982

Apomorphine-induced facilitation of intracranial self-stimulation following dopamine denervation of the nucleus accumbens.

Two groups of rats were trained to lever press for intracranial self-stimulation (ICSS) from electrodes aimed at the posterior lateral hypothalamus or at the region of the locus coeruleus. Following stabilization of baseline responding using descending rate/intensity functions, bilateral 6-hydroxydopamine (6-OHDA) lesions to the nucleus accumbens (N.Acc.) were performed. Subsequent injections of apomorphine (SC) resulted in significant increases in self-stimulation in both lesion groups and significant decreases in self-stimulation in both groups of sham operated animals. These results indicate that the destruction of the dopaminergic terminals in the nucleus accumbens results in a "supersensitive" enhancement of the ICSS stimulating properties of apomorphine regardless of the electrode placement. Both lesion groups also showed a pronounced increase in locomotor activity in photocell cages following treatment with the same dose of apomorphine. These results complement previous work showing that dopamine destruction affects ICSS regardless of electrode placement and support the hypothesis that the midbrain dopamine systems have a general response enabling role in reinforced behavior.

Animals↗
PubMed1981

Evidence for an interaction of opioid and noradrenergic locus coeruleus systems in the regulation of environmental stimulus-directed behavior.

The roles of opioid and noradrenergic (NE) dorsal bundle systems in an animal's response to particular environmental stimuli were examined in a multicompartment exploration chamber. The opiate antagonist naloxone (NAL) produced a stereo-specific increase in environmental stimulus interaction, while the opiate agonist morphine induced a NAL-reversible reduction in stimulus contact. Thus, a specific opioid role in environmental stimulus-directed behavior is indicated. Several reports suggest inhibitory actions of opioids on NE locus coeruleus (LC) activity. Consistent with these reports, we observed that 6-hydroxydopamine (6-OHDA) lesions of the NE dorsal bundles of the LC produced a morphine-like reduction in stimulus contact. Naloxone, which increased stimulus interaction in sham-lesioned rats, had no effect in dorsal bundle lesioned animals. These findings indicate an interaction between opioid and LC systems in the regulation of environmental stimulus-directed behavior.

Animals↗
PubMed1981

Adrenal steroid-induced changes in beta-adrenergic receptor binding in rat hippocampus.

Bilateral 6-hydroxydopamine (6-OHDA) lesions of the dorsal noradrenergic bundle have been shown to increase [3H]dihydroalprenolol (DHA) binding in the rat hippocampus. The effect of adrenalectomy on this increase in receptor binding was examined. Groups of rats received stereotaxically placed 6-OHDA injections aimed at the dorsal bundle (DB) or vehicle injections (control). Half of each group subsequently received bilateral adrenalectomies (ADX) and the other half received sham operations, yielding four groups: control, DB, ADX, and DB + ADX. The DB lesions produced a 41% increase in maximum binding in close agreement with a previous report. No statistically significant change in [3H]DHA receptor binding was observed following adrenalectomy treatment alone. By contrast, the DB + ADX group showed a significant increase in maximum [3H]DHA receptor binding compared to the DB group. This adrenalectomy-induced increase was reversed after 1 week of corticosterone treatment (1.0 mg/kg/12 h, s.c.). These results suggest an interaction between noradrenergic mechanisms and corticosterone in the hippocampus.

Adenylyl Cyclases↗
PubMed1979

Plasma lipoprotein changes in suckling and weanling rabbits fed semipurified diets.

The distribution and composition of the plasma lipoproteins were studied in suckling rabbits and in rabbits either weaned to or fed as young adults cholesterol-free, semipurified diets containing protein of animal (casein) or plant (soy protein isolate) origin. The raised cholesterol levels of the suckling period resulted in an increase of very low density and intermediate density lipoproteins in a making similar to that seen in adult rabbits fed a high fat diet supplemented with cholesterol. Young rabbits fed the cholesterol-free, semipurified, diet containing casein also became hypercholesterolemic but, in this case, the increased cholesterol was found primarily in lipoproteins of intermediate density. Cholesterol levels remained low in those rabbits fed the soy protein isolate diet, and the lipoprotein distribution was somewhat similar to that of chow-fed animals. It appears that the raised cholesterol levels during the suckling period result in different lipoprotein patterns to those produced in young adult animals by a cholesterol-free, semipurified diet.

Aging↗
PubMed1979

Interaction of brain noradrenaline and the pituitary-adrenal axis in learning and extinction.

The effect of 6-hydroxydopamine-induced degeneration of the dorsal tegmental noradrenergic (NA) projection alone or in combination with the removal of the adrenal glands was examined on several behavioral tasks. No impairment of acquisition on a continuously reinforced lever pressing response for food reward was seen as a result of the combined treatment. However, resistance to extinction was observed after depletion of forebrain noradrenaline on its own and this effect was prevented by the adrenalectomy. Adrenalectomy on its own failed to affect extinction. Acquisition of a passive avoidance task was slightly impaired after forebrain noradrenaline depletion but only the group with combined noradrenaline loss and adrenalectomy showed a 24 hour retention deficit. No alteration in shock thresholds was found in any group although both adrenalectomized groups consumed less food and were slightly less active in locomotor cages. It is suggested that previous reports of acquisition and retention deficits in avoidance tasks after combined dorsal NA bundle lesions and adrenalectomy are due to alterations in fear motivation rather than to a general learning impairment.

Animals↗