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Biomedical subjects

R M Zacharko

Publications and source records attributed to R M Zacharko.

50 records · Page 3Linked to original sources
PubMed1982

Preference for fixed vs self-selected durations of brain stimulation in rats administered D-amphetamine sulphate.

Rats implanted with stimulating electrodes in the region of the lateral hypothalamus were allowed the opportunity to respond on (a) a fixed duration lever (b) a variable duration lever or (c) were given a choice between responding on either the lever that delivered the fixed duration of electrical brain stimulation or the lever that allowed the animal to control the duration of electrical brain stimulation. Amphetamine increased rates of responding in both the fixed and variable duration conditions but total duration of brain stimulation was comparable in the two conditions. When given a choice of levers, rats did not prefer either the fixed or variable duration lever. After treatment with d-amphetamine, however, a marked preference for the variable duration lever was observed, although total duration of brain stimulation received in the choice procedure was comparable to that received when either the fixed or variable levers were presented alone. These findings were discussed in terms of brain stimulation preference following amphetamine and its relationship to reward value in the rat.

Animals↗
PubMed1982

Stimulus change influences escape performance: deficits induced by uncontrollable stress and by haloperidol.

Exposure to uncontrollable foot-shock or treatment with haloperidol was found to disrupt subsequent escape behavior. Performance among naive mice, as well as mice that had been exposed to inescapable shock or treated with haloperidol could be enhanced by either interrupting the shock train during escape testing or by presentation of a novel stimulus. The effectiveness of these treatments were dependent on the time at which the change in stimulation occurred. That is, shock interruption or cue presentation just prior to escape being possible enhanced performance, but the same manipulation several seconds prior to escape being possible had only a limited effect. In addition, the time of cue termination also influenced escape behavior. When cue offset coincided with or followed successful escape a performance enhancement was evident, but when cue offset occurred several seconds prior to escape, performance was not affected. It was suggested that inescapable shock and haloperidol treatment hinder performance by disrupting response maintenance. Shock interruption and novel cue presentation minimize disturbances of escape performance by altering the course of the decline of shock-elicited activity.

Animals↗
PubMed1982

Avoidance performance, cue and response-choice discrimination after neuroleptic treatment.

The effects of pimozide on discriminated avoidance performance in a Y-maze were evaluated in mice. Relatively low doses of pimozide (0.4 mg/kg) retarded acquisition of an active avoidance response. The avoidance deficit induced by this dosage was largely eliminated among mice that had received either 1 or 2 previous avoidance training sessions, but was still evident in mice treated with a higher drug dosage (0.8 mg/kg). If mice were initially trained in the drug condition, the disruptive effects were still evident in a later test conducted in the absence of the drug treatment. In contrast to the avoidance deficits, pimozide did not disrupt the acquisition or the performance of a cue- or response-choice discrimination. That is, once a running response was initiated (on avoidance trials) pimozide treated animals appeared capable of appropriately directing the response. It is suggested that at the dosages used pimozide did not affect S-S learning or learning response-outcome contingencies, but rather hindered performance owing to deficits in response initiation processes. Moreover, within a task involving aversive motivation pimozide did not appear to reduce the reinforcement derived for correct responding.

Animals↗
PubMed1980

Response sensitization and depression following long-term amphetamine treatment in a self-stimulation paradigm.

The effects of long-term amphetamine treatment were evaluated on responding supported by self-stimulation of the substantia nigra. Rats repeatedly treated with d-amphetamine, and tested with a low dose of the drug that ordinarily has no behavioral effect, showed higher response rates than animals repeatedly treated with saline and tested with the same dose of amphetamine. In contrast, a depression in responding was observed among animals that received long-term amphetamine administration and were tested with saline. The effects of long-term amphetamine treatment on self-stimulation could not be explained by the intrusion of drug-induced competitive behaviors such as locomotor activity and stereotypy. The results were attributed to changes in dopamine neurotransmission following prolonged exposure to amphetamine and were also discussed in terms of an animal model for 'amphetamine psychosis' and 'postamphetamine depression' in man.

Amphetamine↗
PubMed1980

Intracranial self-stimulation in mice using a modified hole-board task: effects of d-amphetamine.

Mice implanted with stimulating electrodes in the lateral hypothalamus demonstrated reliable self-stimulation rates when given the opportunity to break a photobeam in a modified hole-board task. Self-stimulation rates were enhanced by low dosages of d-amphetamine but were depressed by high dosages. The dose-dependent effects of amphetamine could not be accounted for by changes in exploratory hole-board activity and were discussed in terms of an interaction between the rewarding properties of electrical brain stimulation and the reinforcing properties of amphetamine administration.

Animals↗
PubMed1980

Post-amphetamine depression of self-stimulation responding from the substantia nigra: reversal by tricyclic antidepressants.

The effects of long-term amphetamine treatment were examined on self-stimulation responding from the substantia nigra. Rates of self-stimulation responding were substantially depressed among rats chronically treated with amphetamine and tested in the absence of the drug. When rats were subsequently retested after a two day hiatus in which they received imipramine or amitriptyline, the post-amphetamine depression of rates of self-stimulation responding was mitigated. The efficacy of imipramine and amitriptyline in reversing the post-amphetamine depression of self-stimulation responding was also evident during a continuation of the drug (imipramine or amitriptyline)/test sequence, for seven test sessions. The results of the present investigation were related to changes in dopamine and acetylcholine neurotransmission following long-term amphetamine treatement.

Amitriptyline↗
PubMed1979

Facilitation of self-stimulation with high doses of amphetamine in the rat.

Rats were trained to self-stimulate by interrupting a photobeam and brain stimulation was maintained for as long as the beam of light was broken. d-Amphetamine sulphate was then administered and response rate and total duration of stimulation were recorded. Both response rate and total duration were elevated by 1.0, 2.0, and 5.0 mg/kg dosages. The 1.4 s/response duration observed with saline was elevated to 2.0 s/response with 2.0 and 5.0 mg/kg doses. It was concluded that amphetamine's effects on self-stimulation are at least partially determined by the response requirements of the task employed.

Animals↗
PubMed1979

Thiamin deprivation in ventromedial hypothalamic hyperphagic rats: anorexia, specificity of food aversion, and a dietary consideration.

The anorexic consequence of thiamin deprivation was investigated in ventromedial hypothalamic (VMH) hyperphagic rats under either high-fat or low-fat thiamin-free diet conditions. The low-fat diet maintained feeding significantly longer in thiamin-deprived VMH rats than in intact rats, whereas the hig-fat diet sustained feeding in thiamin-deficient intact rats and accelerated anorexia onset in vitamin B1 deprived VMH rats. This effect was noted under both ad lib and pair-feeding conditions. Thiamin-deprived VMH rats subjected to weight control developed anorexia sooner than intact subjects regardless of the diet employed. The VMH rats fed a high-fat diet failed to resume feeding after thiamin readministration, which was interpreted as a permanent aversion to this diet. The relation between dietary intake and conditioned taste aversion is discussed with reference to the VMH and intact rat.

Animals↗
PubMedDate not supplied

The impact of stressors on immune and central neurotransmitter activity: bidirectional communication.

Antigenic challenge may have broad ranging effects which include not only immunological changes, but also endocrine and central neurotransmitter repercussions, and may thus elicit profound behavioral sequelae. Commensurate with the notion that bidirectional communication exists between the immune and central nervous systems it has been demonstrated that manipulations which influence central neurotransmitter or endocrine activity provoke alterations of immune functioning, and conversely immunological alterations will affect central neurotransmitter and endocrine activity. It seems, as well, that environmental stressors may provoke marked alterations of the activity of each of these systems. Indeed, in several respects the variables that influence vulnerability to stressor-provoked neurotransmitter changes, likewise affect the immunological alterations engendered by stressors. Moreover, immunological challenges will affect central neurotransmitter functioning in much the same way as stressors provoke such effects. It is thought that immune derived products (including cytokines as well as peptide hormones) may act directly or indirectly to moderate neurotransmitter functioning, and centrally derived neurotransmitters and hormones may affect receptors present on lymphocytes. In accordance with earlier suggestions, it is maintained that the immune system may be acting as a sensory organ informing the brain of the presence of antigenic challenges, and the brain may interpret such challenge as a stressor, hence leading to behavioral alterations.

Animals↗
PubMedDate not supplied

Behavioral, neurochemical, anatomical and electrophysiological correlates of panic disorder: multiple transmitter interaction and neuropeptide colocalization.

Neurochemical accounts of panic disorder focus on peripheral indices of central transmitter activity, hormonal correlates and therapeutic efficacy. Anxiogenic agents augment norepinephrine activity, some anxiolytics increase serotonin neurotransmission while benzodiazepines and antidepressants influence catecholamine, indoleamine and gamma-aminobutyric acid turnover in infrahuman subjects. Reliable correlates of central transmitter activity in panic disorder are not in evidence. While animal models of anxiety may not mirror the symptom profile of panic, neurobiological accounts of panic disorder fail to consider extensive central colocalization of neurotransmitter and putative neurotransmitters. In effect, transmitter release in major ascending and descending transmitter systems is modulated by variable neuropeptide interfacing. The behavioral concomitants of psychological disturbance likely follow from variable neurochemical release induced by stimuli as well as conditioning and sensitization. The functional role of receptor sites associated with multiple neurochemical systems may vary and the sensitivity and/or density of receptor sites may be modified. Accordingly, the behavioral and neurochemical concomitants of acute and chronic pathology may be fundamentally different from one another. The present review argues that the symptoms of panic disorder and the etiology of the illness must be evaluated against a background of genetic, organismic and experiential factors. Such variables presumably underlie the diverse behavioral symptoms associated with panic disorder and variations in the therapeutic efficacy of pharmacological treatment.

Animals↗