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F Weiss

Publications and source records attributed to F Weiss.

At least 19 recordsLinked to original sources

Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration.

The effects of withdrawal from cocaine on extracellular dopamine (DA) levels in the nucleus accumbens (NAC) were examined by intracranial microdialysis in awake rats after periods (9.5-21.75 h) of unlimited-access, intravenous cocaine self-administration. Cocaine withdrawal was associated with significant reductions in basal DA overflow that persisted up to 12 h. Maximal inhibition of DA release (mean +/- S.E.M. 66.15 +/- 3.30 percent of basal levels) was observed between 4-6 h after cessation of cocaine intake and was positively correlated (r = 0.88) with the duration of the preceding self-administration episode. The results suggest that suppression of basal DA release in the NAC is an adaptive consequence of sustained cocaine exposure and may in part underlie the post-cocaine anhedonia observed in behavioral models of cocaine withdrawal.

Animals

Neuropharmacology of cocaine and ethanol dependence.

Drug addiction includes two important characteristics, chronic compulsive or uncontrollable drug use and a withdrawal syndrome when use of the drug is stopped. Animal models for the motivational components of drug dependence have been developed allowing a systematic exploration of the neurobiological mechanisms of drug dependence. The reinforcing actions of acute cocaine as measured by intravenous cocaine self-administration appear to be mediated by the presynaptic release of dopamine in the region of the nucleus accumbens and may preferentially involve the dopamine D-1 receptor subtype. The nucleus accumbens circuitry involved in the reinforcing actions of cocaine may include the ventral pallidum and may be modulated by serotonin. Chronic cocaine produces increases in brain reward thresholds that may reflect the "dysphoria" and anhedonia associated with cocaine dependence and suggests a dysregulation of brain reward systems possibly involving dopamine. Reliable measures for the acute reinforcing effects of ethanol in nondependent animals have been established in the rat using a lever press operant and a taste habituation procedure. Important roles have been established for serotonin, GABA, dopamine, and opioids in the acute reinforcing properties of ethanol, perhaps acting on some of the same neural circuitry subsuming the reinforcing actions of other drugs of abuse. Studies of the motivational aspects of ethanol dependence have suggested a functional role for brain corticotropin-releasing factor. These results suggest that the neurobiology of drug dependence involves not only neurotransmitters that mediate the acute reinforcing properties of drugs, but also the aversive motivational and emotional aspects of drug withdrawal. Advances in our understanding of brain changes associated with the switch from acute effects to chronic actions may provide a key to our understanding of not only drug dependence, but also psychopathology such as, anxiety, and affective disorders.

Alcoholism

Increases in extracellular dopamine in the nucleus accumbens by cocaine are inversely related to basal levels: effects of acute and repeated administration.

Repeated administration of cocaine enhances several of the behavioral and neurochemical responses to subsequent cocaine injections, an effect that has been attributed, in part, to decreased somatodendritic autoreceptor sensitivity of mesocorticolimbic dopamine (DA) neurons. Such changes in autoregulation may not only modify the direct effects of cocaine on extracellular DA levels but also result in tonically increased basal DA release in the terminal areas of the mesocorticolimbic DA system. The present study was therefore designed to investigate the effects of repeated cocaine administration on basal extracellular DA concentrations in the nucleus accumbens (NAC) using in vivo microdialysis procedures in halothane-anesthetized rats. We subsequently examined the relationship between basal DA levels and the increase in extracellular DA produced by an acute injection of cocaine, and determined whether this relationship was altered by prior, repeated exposure to cocaine. Rats received one daily intraperitoneal injection of cocaine (30 mg/kg) or its vehicle (saline) for 10 consecutive days. On days 1, 3, or 7 after termination of the repeated cocaine treatment, extracellular DA levels in the NAC were determined under basal conditions and following a single intraperitoneal cocaine challenge injection (10 mg/kg) in separate groups of rats. Repeated cocaine administration produced a substantial increase in basal DA release in the NAC that was most prominent on day 1 post-cocaine (mean +/- SEM: 10.7 +/- 2.55 nM vs 3.55 +/- 0.56 nM) but was no longer apparent on day 7 post-cocaine. Higher extracellular DA levels were also observed after cocaine challenge in rats that received repeated cocaine treatments. Similar to the increase in basal release, this effect was most pronounced on day 1 post-cocaine (23.6 +/- 4.36 nM vs 12.61 +/- 1.76 nM) but did not persist through day 7 post-cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The influence of cocaine self-administration on in vivo dopamine and acetylcholine neurotransmission in rat caudate-putamen.

Presynaptic dopamine and acetylcholine transmission in the anteroventral (limbic) caudate-putamen were studied by microdialysis in freely moving rats during cocaine self-administration sessions. Acute cocaine exposure elevated dopamine (DA) overflow in drug-naive animals. However, during repeated cocaine administration, the drug-induced elevation of DA was attenuated in animals previously exposed (during the prior 9 days) to cocaine. The diminished dopamine response in repeatedly treated animals while self-administering cocaine was speculated to be due to increased activity of DA transport carrier and/or supersensitive receptors modulating DA release. During repeated cocaine administration, extracellular acetylcholine levels in animals previously exposed to cocaine were found to be significantly decreased compared with controls. The findings of the study may suggest a functional development of supersensitive DA receptors postsynaptic to the DA terminal (located on cholinergic neurons) as a consequence of previous cocaine exposure. Such supersensitivity would allow for a reduced DA signal to be amplified at the postsynaptic level during repeated cocaine self-administration.

Acetylcholine

Free-choice responding for ethanol versus water in alcohol preferring (P) and unselected Wistar rats is differentially modified by naloxone, bromocriptine, and methysergide.

The role of opioids, dopamine and serotonin in ethanol (EtOH) reward and preference was investigated in non-deprived, Alcohol-Preferring (P), and genetically heterogenous Wistar rats. Operant responding for ethanol was initiated using sweet-solution substitution procedures. The rats were then trained in 30-min daily sessions to respond for ethanol (10% v/v) versus water under a two-lever, free-choice contingency. All testing was conducted in the absence of water and food deprivation or addition of sweeteners to the ethanol drinking solution. Rats of both strains developed stable preferences in responding for ethanol over water and consumed ethanol at quantities sufficient to produce pharmacologically relevant mean blood alcohol concentrations (P-Rats: 98 +/- 19.6 mg%; unselected Wistars: 41.7 +/- 8.5 mg%). In P-rats, systemic naloxone (NAL; 0.125, 0.25 and 0.5 mg/kg) pretreatments resulted in a dose-dependent suppression in responding for both ethanol and water, but did not alter ethanol preference (expressed as percent ethanol of total intake). In contrast, bromocriptine (BRO; 1.0, 2.0 and 4.0 mg/kg) produced a significant, dose-dependent shift in preference from ethanol toward water by inhibiting responding for ethanol while enhancing water consumption. In unselected Wistar rats, NAL and BRO treatments produced changes in ethanol preference patterns similar to those observed in P-rats. However, compared to P-rats, these changes were smaller and not consistently dose dependent. No changes in ethanol preference and water or ethanol intake were observed with methysergide (MET; 2.5, 5.0, 10.0 mg/kg) in either strain of rat. Together, the results suggest a possible involvement of dopaminergic mechanisms in the reinforcing properties of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking

Cocaine reinforcement and extracellular dopamine overflow in rat nucleus accumbens: an in vivo microdialysis study.

Addictive properties of cocaine have been suggested to be mediated by an interplay of depletion (craving) and re-elevation (reinforcement) of dopamine (DA) levels in limbic brain area. In this study, direct measurement of dopamine in the extracellular fluid of rats freely self-administering cocaine was evaluated using in vivo microdialysis. Acute cocaine administration was associated with enhanced accumulation of DA in the nucleus accumbens, correlated with enhanced locomotor activity. In contrast, the increased DA overflow observed in drug-naive animals was attenuated in animals self-administering cocaine who had previous regular repeated (9-day) exposure to the drug. The results suggest that the absolute amount of DA in the extracellular space is not the critical factor correlated with the self-administration behavior. Additionally, the results indicate that the reduced ability of cocaine to re-elevate DA to first-time drug use is not due to a reduction of DA in the tissue or reduced DA synthesis, but may instead be associated with alterations of release and reuptake processes.

Animals

CCK-8 injected into the nucleus accumbens attenuates the supersensitive locomotor response to apomorphine in 6-OHDA and chronic-neuroleptic treated rats.

Postsynaptic dopamine-cholecystokinin (CCK) interactions in the nucleus accumbens were studied in two behavioral preparations of DA receptor supersensitivity: chronic-neuroleptic treated and 6-hydroxydopamine (6-OHDA) denervated rats. Subcutaneous (SC) injections of apomorphine (APO; 0.15 mg/kg) in experiment 1 produced marked hyperlocomotion in rats following 12 days of pretreatment with cis-[Z]-flupenthixol (2 mg/kg; twice per day). Bilateral intra-accumbens (N.Acc.) microinjections of CCK-8 (2 ng and 2 micrograms) reliably reduced APO-stimulated hyperlocomotion. An intermediate CCK dose (20 ng) was without effect. No change in APO responsivity following chronic vehicle treatment was observed and the baseline APO response was not altered by CCK at any dose. Denervation of mesolimbic dopamine (DA) terminals by intra-N.Acc. injections of 6-hydroxydopamine (6-OHDA; 8 micrograms/side) in experiment 2 similarly resulted in intense locomotor hyperactivity after APO stimulation (0.1 mg/kg; SC). Bilateral intra-N.Acc. injections of CCK-8 (1, 10, 100 ng, and 1 micrograms) significantly attenuated the supersensitive locomotor response to APO. As in experiment 1, CCK produced "biphasic" dose-response effects with strong attenuation that persisted throughout the entire 60-min test at both high (1 microgram) and low (1 ng) doses. Intermediate CCK doses (10 and 100 ng) produced only short-term reductions in activity. Hypomotility induced by APO in SHAM-lesioned rats was not effectively reversed by CCK treatments. CCK had no effect on unstimulated baseline locomotor activity in either 6-OHDA or SHAM-lesioned rats. These results provide further evidence that CCK-8 modulates mesolimbic DA activity by functionally opposing the postsynaptic effects of DA in the region of the nucleus accumbens.

Animals

Opposite actions of CCK-8 on amphetamine-induced hyperlocomotion and stereotypy following intracerebroventricular and intra-accumbens injections in rats.

Cholecystokinin-octapeptide (CCK-8) has recently been found to coexist with dopamine (DA) in a subpopulation of midbrain DA neurons. The present study investigated the functional nature of this coexistence by testing the effects of intracerebroventricular (ICV) and intra-nucleus accumbens (NAS) applications of CCK-8 in two behavioral assays of DA function (i.e., stimulant-induced hyperlocomotion and stereotypy). Rats were injected with 1 or 3 mg/kg of d-amphetamine sulfate (AMP) 15 minutes prior to ICV (2 micrograms) or intra-NAS (20 ng, 200 ng, or 2 micrograms) injections of CCK-8 or haloperidol (HAL; 5 micrograms). ICV administered CCK-8 was found to antagonize the locomotor stimulatory effects of the low AMP dose, while the same peptide treatment markedly potentiated the stereotypy produced by the high dose of AMP. Similar results were obtained when CCK-8 was microinjected directly into the NAS, with the strongest effects observed following the smallest (i.e., 20 micrograms) dose. These results suggest that both locomotor-antagonizing and stereotypy-potentiating effects of central CCK application depend on CCK-DA interactions in the nucleus accumbens.

Amphetamine

Comparison of circling induced by unilateral intrastriatal microinjections of haloperidol, clozapine and CCK-8 in rats.

The existence of the neuropeptide cholecystokinin (CCK) within a subpopulation of central dopamine (DA) neurons has led to speculations that the peptide may serve as an endogenous modulator of DA functions. To test this possibility, the present study examined the pharmacological action of CCK-8 by comparing its effects on DA-mediated circling behavior with those of a typical (haloperidol; HAL) and an atypical (clozapine; CLZ) dopamine antagonist neuroleptic drug. Rats received unilateral intrastriatal infusions of either sulfated CCK-8 (1, 2, or 8 micrograms), HAL (5 micrograms) or CLZ (5 or 20 micrograms) 15 minutes after systemic injection of d-amphetamine (1 mg/kg). Animals were then placed into rotational chambers where the number and direction of complete 360 degree turns was automatically recorded over a 1 hour session. HAL produced strong and almost exclusive ipsilateral circling while the responses after CLZ and CCK-8 were reliably more variable in rotational direction. More specifically, the results suggest that CLZ is only a weak antagonist of behaviors mediated by striatal DA activation while CCK seems to be devoid of antidopaminergic properties in the striatum.

Animals

Body-image disturbances among obese adults: evaluation and treatment.

This paper describes how to diagnose and treat body-image disturbances by a clinical technique involving direct patient participation. The technique has been effective as a diagnostic barometer uncovering discrepancies between the reality of being fat and some patients' secret belief of being thin.

Adult

An improved method for adrenalectomy of suckling rats. The influence of thrombin treatment and deoxycorticosterone substitution on survival and on hepatic and renal enzyme activities.

Adrenalectomy of suckling rats is complicated by a high mortality rate, caused by the loss of blood (early mortality) and by the disturbed sodium-potassium balance (late mortality). Treatment of the abdominal cavity with a thrombin solution and a daily administration of deoxycorticosterone glucoside (DOC) decrease the total mortality remarkably. DOC treatment has no influence on renal beta-glucosidase and beta-galactosidase as well as on hepatic tyrosine aminotransferase activity, whereas hepatic serine dehydratase activity exhibits a time- and dosage-dependent response to this hormone. The DOC effect is very likely a consequence of the glucocorticoid-like action of the synthetic hormone, which competes with the endogenous glucocorticoids for the hepatic receptor molecules.

Adrenal Glands

Properties of retrovirus-like particles produced by a human breast carcinoma cell line: immunological relationship with mouse mammary tumor virus proteins.

Clonal derivatives 8 and 11 of the T47D human breast carcinoma cell line release particles that have the biochemical characteristics of a retrovirus. Particles recovered from cultures of [3H]uridine-labeled clone 11 had a density of 1.18 g/ml and contained 60-70S and 35S RNAs associated with reverse transcriptase activity. The production of these particles was steroid-dependent. Clone 8 particles had a higher density, 1.195 g/ml, and their production was independent of steroid hormone. By RIA, antigens crossreactive with the 52,000-dalton envelope glycoprotein gp52, the major external protein of mouse mammary tumor virus, were found associated with these particles and in the media. Most of the gp52-related antigen was in soluble form, but it was enriched in the particle preparation. A lesser amount of antigen was distributed within the cultured cells. Absorption of rabbit antibody to gp52 with clone 11 particle preparations eliminated the ability of this antibody to detect immunocytochemically a crossreactive antigen previously localized in tissue sections of human breast carcinoma. These results indicate that the particle isolates from T47D contain the same gp52-related antigen found in human breast carcinomas and constitute an excellent source for the purification and characterization of this antigen.

Breast Neoplasms

Design and biomechanical evaluation of a cementable endosteal blade implant.

A cementable endosteal blade implant has been developed and evaluated. Inherent in the design are the following factors: minimization of stress concentrators, ease of implantation, and high resistance to loosening. Other potential advantages of this design as compared with conventional endosteal blade implants include reduced hazards of postoperative infection and reduced likelihood of metallic corrosion. Six conventional endosteal implants and six cementable implants were installed in steer mandibles using standard dental surgical techniques and Simplex-brand methyl methacrylate bone cement. They were loaded in uniaxial compresstion at a loading rate of 0.0122 in./min. the stiffness (S), deformation at 900-lb load (D900), proportional limil (PL), and load at 0.04 in. deformation (L0.04) were calculated for each test. The cementable design showed a twofold increase in stiffness, only 17% of the deformation at 900lb, more than twice the proportional limit, and at least twice the load at 0.04 in. deformation when compared with similar values for the conventional endosteal implants. This study reveals that, in addition to being unstable in bone, conventional endosteal implants are also unstable when used with acrylic bone cement. The new design should eliminate most of the problems associated with endosteal blade implantation.

Animals