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Biomedical subjects

F G Graeff

Publications and source records attributed to F G Graeff.

At least 109 records · Page 6Linked to original sources
PubMed1981

Effect of minor tranquilizers, tryptamine antagonists and amphetamine on behavior punished by brain stimulation.

Earlier observations have shown that septal lesions released operant responding punished by foot-shock, but did not change behavior punished by electrical stimulation of the dorsal periaqueductal gray (DPAG) substance of the rat brain. In contrast, chlordiazepoxide facilitated both kinds of punished responding. In order to further study the mechanism of brain stimulation punishment, dose-response curves of two minor tranquilizers, chlordiazepoxide and pentobarbital, of two tryptamine antagonists, methysergide and cyproheptadine as well as of amphetamine on lever-pressing behavior of rats maintained by water reinforcement and punished by DPAG stimulation were determined. A multiple schedule with a variable-interval 2 min (VI 2) non-punished component and a continuous reinforcement (CRF) component in which every response was both rewarded and punished was used. Chlordiazepoxide and pentobarbital caused dose-dependent increases in punished responding. Unpunished VI response rates were also moderately increased by the minor tranquilizers. In contrast, neither methysergide nor cyproheptadine increased punished or unpunished responding at doses that have been previously shown to markedly release behavior punished by foot-shock, in the rat. Conversely, amphetamine, a drug that usually does not release responding punished by peripheral noxious stimulation, caused dose-dependent increases in responding suppressed by DPAG punishment without affecting VI response rate. These and previous results with septal lesions suggest that neither the septo-hippocampal system nor its serotonergic input from the mesencephalon mediate response suppression by DPAG electrical stimulation, in contrast to their active role in peripheral punishment. This difference may also explain the marked facilitatory effect of amphetamine on responding punished by brain stimulation shown by the present results.

Amphetamine↗
PubMed1981

Minor tranquilizers and brain defense systems.

In this article the participation of different brain neuron systems in the integration of fear responses, and in the anti-anxiety action of minor tranquilizers (MT) is discussed. As necessary background, the molecular mechanisms of MT action disclosed by recent neurochemical research are briefly described. The reviewed evidence suggests that MT decrease anxiety by impairing the functioning of brain neuron systems integrating defensive behavior. These systems are the septo-hippocampal system, together with its afferent mono-aminergic input from the rostral brain stem, which commands behavioral inhibition arising in situations involving threat of punishment or frustration. In addition, the brain aversive system comprising the dorsal periaqueductal gray matter, the periventricular gray matter and the amygdala integrates the active defense patterns of fight or flight as well as elaborates aversive motivation. The depressant action of MT upon both defense systems may be primarily due to facilitation of neurotransmission mediated by gamma-aminobutyric acid (GABA).

Animals↗
PubMed1981

Depressant action of chlordiazepoxide on cardiovascular and respiratory changes induced by aversive electrical stimulation of the brain.

1. Electrical stimulation of the dorsal periaqueductal gray matter (DPAG), an aversive area of the rat brain, increased the mean blood pressure of awake rats as well as of animals anesthetized with urethane. 2. In the anesthetized rats, increases in heart rate and in breath rate were also induced by DPAG stimulation. 3. Chlordiazepoxide, a benzodiazepine, decreased the blood pressure rise caused by aversive stimulation of the brain in the awake rat. 4. Chlordiazepoxide elicited the same effect in urethane-anesthetized rats. In addition, the hyperpnea induced by electrical stimulation of the dorsal periaqueductal gray matter was also decreased by the drug. 5. The pressor response to intravenous noradrenaline was not affected by chlordiazepoxide. 6. These results suggest that benzodiazepines attenuate the neurovegetative changes accompanying emotion by depressing brain systems that integrate emotional behavior.

Animals↗
PubMed1980

Dorsal periaqueductal gray punishment, septal lesions and the mode of action of minor tranquilizers.

In order to study the role of the septo-hippocampal system and the dorsal periaqueductal gray (DPAG) substance in punished behavior and in the action of minor tranquilizers, two groups of rats were trained to lever press on a continuous reinforcement schedule of food presentation. In one group, every response was subsequently punished by foot-shock delivery; in the other, by brief electrical stimulation of the DPAG of the mesencephalon. In both groups response rats were reduced to less than 10% of pre-punishment rates, but not completely supressed. Response rates did not significantly differ between the two groups, either before or after the introduction of punishment. Septal lesions significantly increased responding in the animals punished by foot-shock, but did not affect responding suppressed by DPAG stimulation. Injection of chlordiazepoxide (5mg/kg,IP) significantly increased punished responding in both groups of rats, before as well as after the septal lesion. Before the septal lesion was made, responding suppressed by foot-shock was significantly more released by chlordiazepoxide than responding punished by DPAG stimulation. These results suggest that in punishment tests using foot-shock, both a behavioral inhibitory system, including the septo-hippocampal structures and an aversive or punishment system, including the DPAG substance, act together to produce response suppression. Both these systems would be depressed by minor tranquilizers in order to cause their anti-punishment and perhaps their anti-anxiety action as well.

Animals↗
PubMed1979

Effect of amphetamine on nondiscriminated key-pecking avoidance in pigeons.

Dose-effect curves for amphetamine on key-pecking behavior of pigeons maintained by two-component multiple schedules of shock postponement were determined. During the first experimental phase the response-shock interval (RS) was held constant and the shock-shock interval (SS) varied. Under these conditions, shock rate was greater during the component with the shorter SS. However, response rates were comparable in both components. Also, the magnitude of the response rate increments caused by appropriate doses of amphetamine during both schedule components were similar. During the second experimental phase, the SS was held constant and the RS varied. As a consequence, baseline response rate was considerably lower in the component with the longer RS than in the short RS component. Shock presentations were also less frequent during the former than during the latter component, but the differences in shock rate between the components were comparable or smaller than those observed during the first experimental phase. Under these conditions, the effects of amphetamine in the two schedules components were markedly different, lower response rates being considerably more increased than higher rates.

Amphetamine↗
PubMed1978

Role of the periaqueductal gray substance in the antianxiety action of benzodiazepines.

In order to study the interactions between serotonergic mechanism and electrical stimulation of the mesencephalic central gray substance, rats were trained to lever-press for terminating aversive electric stimuli applied at the Periaqueductal gray and adjoining tectum of the mesencephalon. Experimental sessions consisted of 40 discrete escape trials of a maximum of 30 sec duration, separated by 30 sec intervals. Dose-effect curves of two tryptamine antagonists, cyproheptadine and methysergide, as well as of the benzodiazepine minor tranquilizer, chlordiazepoxide, on average escape latencies and on frequency distribution of individual latencies were determined. Doses of 3 to 10 mg/kg of cyproheptadine decreased average latencies of escape responding in six of eight rats studied. Doses of 10 and 30 mg/kg of methysergide also facilitated escape responding in one of three rats. In contrast, doses from 1 to 10 mg/kg of chlordiazepoxide, that cause little sedation or ataxia, produced dose-dependent increases in escape latencies. Furthermore, doses of 5.6 and 10 mg/kg of chlordiazepoxide partially blocked escape responding. The facilitatory effects of the tryptamine antagonists suggest that escape behavior is inhibited by brain tryptaminergic mechanisms, whereas the specific depressant effect of chlordiazepoxide on escape from Periaqueductal gray electrical stimulation suggest that this region may be involved in the antianxiety action of benzodiazepines.

Animals↗
PubMed1977

Effect of tryptamine antagonists on self-stimulation. Interaction with amphetamine.

In order to investigate the role played by serotonergic mechanisms in self-stimulation (SS) behavior, the effects of two tryptamine antagonists, cyproheptadine and methysergide on SS were measured. Also the influence of antitryptaminic drug pre-treatment on the facilitatory effect of amphetamine, a pro-adrenergic drug, on SS was studied. Rats with brain electrodes permanently implanted at the lateral hypothalamus and trained to lever-press for response-contingent brain electric stimulus presentation were used. Stimulus current was maintained at threshold level. Both tryptamine antagonists used potentiated the enhancing effect of amphetamine on low SS rates, displacing to the left its dose-effect curve; cyproheptadine was at least three times more potent than methysergide. In addition, cyproheptadine, but not methysergide, caused dose-related increases in SS rate, when given alone. These results suggest that brain serotonergic systems play an inhibitory role in SS, opposing the facilitatory influence of adrenergic mechanisms.

Amphetamine↗
PubMed1977

Role played by the adenylcyclase-cAMP system of the rat septal area on Na+, K+ and water renal excretion.

In this study, the participation of the adenylcyclase--cAMP system of the rat septal area in the mediation of the natriuretic, kaliuretic and diuretic effects of noradrenaline (NA) was investigated. The intraseptal injection of 20 nmol of NA caused a significant increase in the urinary excretion of Na+ and K+ as well as in the urinary volume during the 2 hr period following the intracerebral injection which was blocked by 40 nmol of phentolamine, locally injected, 30 min before the catecholamine. In contrast, pretreatment with propranolol (100 nmol) potentiated the effects of NA on salt and water renal excretion. The intraseptal injection of 3.12 to 50 nmol of dibutryrl cyclic adenosine monophosphate (db cAMP) caused dose-dependent increase in natriuresis and kaliuresis, but a decrease in urinary volume. Under the same experimental conditions, caffeine administration (6.25 to 100 nmol) also induced dose-dependent increases in Na+ and K+ urinary output. These results indicate that the saluretic effect of NA may be mediated by an alpha receptor-induced activation of the adenylcyclase--cAMP system in the septal area.

Adenylyl Cyclases↗
PubMed1976

Effect of cyproheptadine and combinations of cyproheptadine and amphetamine on intermittently reinforced lever-pressing in rats.

Effects of the tryptamine antagonist, cyproheptadine, as well as of amphetamine, chlordiazepoxide, and combinations of cyproheptadine with amphetamine on lever-pressing behavior of rats were determined. A multiple, fixed-interval, 2 min fixed-ratio, 15 response schedule of water presentation was used. The three drugs affected fixed-interval fixed-ratio responding in a rate-dependent way, lower rates being more increased whereas higher rates were relatively more decreased. Cyproheptadine increased low response rates to a lesser extent than amphetamine, but increased high response rates that were little affected or only decreased by amphetamine. The combination of cyproheptadine and amphetamine increased response rates to a higher extent than either of the drugs alone. In addition, the rate-suppressant effects of the highest doses of amphetamine were also enhanced by cyproheptadine. These results show that cyproheptadine can increase nonpunished responding and suggest that cyproheptadine and amphetamine act synergistically, but through different mechanisms, upon multiple fixed-interval fixed-ratio performance.

Amphetamine↗
PubMed1976

The role of central muscarinic and nicotinic receptors in the regulation of sodium and potassium renal excretion.

The effect of intraseptal injection of carbachol and nicotine on urinary output of Na+ and K+ in untreated rats as well as in animals pretreated with locally injected atropine, hexamethonium, dibenamine and propranolol was studied in order to evaluate the relative role played by central muscarinic and nicotinic receptors in the regulation of salt and water renal excretion. The injection of 30-250 nmol of nicotine into the medial septal area caused a dose-dependent increase in Na+ and K+ urinary output whereas urine volume was little affected. The effect of 30 nmol of nicotine was blocked by pretreatment with 100 nmol of hexamethonium. In addition, pretreatment with 5 nmol of either hexamethonium or atropine partially antagonized the natriuretic and kaliuretic effect of 1 nmol of carbachol. Also the alpha-blocking agent, dibenamine (150 nmol) antagonized, while the beta-blocker, propranolol (100 nmol) significantly enhanced the effect of carbachol. Propranolol (100 nmol) alone caused a small, but significant increase in Na+ and K+ renal excretion. These results indicate that stimulation of both muscarinic and nicotinic receptors in the septal area, as caused by carbachol, elicits increased disposition of Na+ and K+ by the kidneys. Also, part of the effects of carbachol appear to be mediated by the release of endogenous catecholamines, acting on central alpha receptors to increase Na+ and K+ urinary excretion. On the other hand, simultaneous activation of beta-receptors by the released amines would partially inhibit this effect.

Animals↗
PubMed1975

Influence of response topography on the effect of apomorphine and amphetamine on operant behavior of pigeons.

Key-pecking and treadle-pressing behavior were maintained in five pigeons by a mult. FI5 key FI5 treadle schedule of food presentation. Dose-effect curves for apomorphine and amphetamine on overall rates of responding in both F1 componenets of the multiple schedule were determined. Effective doses of apomorphine caused dose-dependent decreases on treadle-pressing rates in all animals. Similarly, key pecking rates were decreased by increasing doses of apomorphine in two of the five pigeons. However, dose-dependent increases in key-pecking rates were caused by apomorphine in the other three birds. In this group of pigeons, the mean key-pecking rate was increased to over 500% of the control rate by the dose of 1 mg/kg of apomorphine. Observation of the animals under the effect of apomorphine showed continuous pecking at the operative key in these three animals while the other two pecked at different places of the floor and walls of the experimental chamber. Appropriate doses of amphetamine caused rate-increasing effects on key-pecking as well as treadle-pressing rates of all pigeons. These results suggest that the increases in key-pecking rate caused by apomorphine in some pigeons in a conventional operant situation due to the orientation of the drug-induced stereotyped pecking toward the response keypecking, as a consequence of the topographic compatibility between this behavioral effect of apomorphine and the operant selected for study.

Amphetamine↗
PubMed1975

Effect of intracerebroventricular bradykinin and related peptides on rabbit operant behavior.

The dose-effect relationships of intraventricularly injected bradykinin, Gly-Arg-Met-Lys-bradykinin (GAML-bradykinin), synthetic substance P and angiotensin II on lever-lifting behavior of rabbits in a variable-interval (VI) 72-second schedule of sweetened water presentation were determined. All peptides used caused dose-dependent decreases in overall rates of VI responding during the experimental session in the following order of potency: angiotensin II greater than bradykinin = substance P greater than GAML-bradykinin. The angiotensin II dose-effect curve was less steep than those of the other peptides. The administration of nearly equimolar doses of the bradykinin potentiating peptides, BPP5a and BPP9a, slightly decreased overall VI response rates and caused a 10- to 20-fold potentiation of the rate-decreasing effect of bradykinin on VI responding. Both angiotensin II and bradykinin caused pauses in responding of dose-dependent duration at the beginning of the experimental session that were followed by normal VI responding. The effect of GAML-bradykinin on VI performance was similar to that of bradykinin and angiotensin II but had a delay of onset of 3 to 6 minutes. In contrast, substance P caused actual decreases in response output and pauses of variable duration interspersed between periods of regular VI responding. At the doses used, both bradykinin-potentiating peptides caused uniform decreases in VI responding throughout the experimental session. Gross behavioral changes caused by the peptides were also observed. After the intraventricular injection of bradykinin or GAML-bradykinin, rabbits showed decreased motility, ptosis, miosis and lowered ears; after angiotensin II, animals remained motionless but with wide open eyes, fully raised ears and no miosis. In turn, substance P caused restlessness and increased locomotion. These results together with reported evidence on other powerful central actions of bradykinin, angiotensin and substance P and on the existence of components of their releasing and destroying enzymatic systems in the brain suggest that linear peptides may play a role in the functioning of the central nervous system.

Angiotensin II↗
PubMed1975

Central site of the hypertensive action of bradykinin.

The intraventricular injection of 1 mug of bradykinin (BK) in rats anesthetized with urethane (1.5 g/kg i.p.) caused an increase in mean arterial blood pressure with little or no change in pulse pressure or heart rate. A similar hypertensive response followed the local administration of 0.5 mug of BK at the pars ventralis of the lateral septal area, whereas local application at other subcortical regions, known to be involved in cardiovascular regulation, caused no effect. Injections of 0.5 or 1 mug of synthetic substance P or 1 mug of 9-desarginine-bradykinin at the pars ventralis of the lateral septal area caused no change in blood pressure. In addition, bilateral electrolytical lesions placed in the lateral septal area either markedly reduced or completely blocked the pressor response to intraventricular BK. These results suggest that the pars ventralis of the lateral septal area is involved in the pressor action of BK in the central nervous system. They also indicate that this brain region responds fairly specifically to BK and that local vascular changes are unlikely to be involved in the mediation of the central action of BK.

Animals↗