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M Cador

Publications and source records attributed to M Cador.

At least 37 records · Page 2Linked to original sources
PubMed1993

Central administration of corticotropin releasing factor induces long-term sensitization to D-amphetamine.

Corticotropin releasing factor (CRF) has been shown to initiate neuroendocrine and behavioral responses to stress. As stress and amphetamine (AMPH) show cross-sensitization, we investigated the role of endogenous CRF in behavioral sensitization to D-AMPH. In order to evaluate the participation of the central action and the pituitary-adrenocortical (PA) stimulatory effect of CRF, we compared the effects of repeated intracerebroventricular (i.c.v.) administration of CRF (0, 0.5, 2.5 micrograms/2 microliters), which have central and neuroendocrine consequences, with those of repeated subcutaneous administration of CRF (0, 0.1, 0.5, 2.5 micrograms/250 microliters), doses which only stimulate the PA axis, on the development of sensitization to AMPH-induced motor activation administered 1 week later. Repeated i.c.v. administration of CRF induced a long-lasting enhancement of the hyperactivity induced by 0.75 mg/kg peripheral administration of D-AMPH, whereas no sensitization to D-AMPH was observed following repeated subcutaneous administration of CRF. These results favor the hypothesis that a centrally mediated action of CRF is involved in the cross-sensitization of psychostimulants and stress.

Animals↗
PubMed1993

Relative roles of ventral striatal D1 and D2 dopamine receptors in responding with conditioned reinforcement.

Several experiments investigated the involvement of D1 and D2 dopamine receptors in the ventral striatum in the control over behaviour by a conditioned reinforcer using an acquisition of new response procedure. Intra-accumbens infusion of either the D1 receptor antagonist, SCH 23390, or the D2 receptor antagonist, raclopride, completely blocked the potentiative effects of intra-accumbens d-amphetamine on responding with conditioned reinforcement and reduced responding to control levels. SCH 23390 was more potent than raclopride. At higher doses in the absence of d-amphetamine, both antagonists also blocked the preference for responding on the lever producing the conditioned reinforcer. Intra-accumbens infusions of either the D1 receptor agonist, SKF 38393, or the D2/3 receptor agonist, LY 171555 (quinpirole), selectively potentiated responding on the lever producing the conditioned reinforcer. Various combined infusions of the D1 and D2 agonists in specific low doses had additive, but not synergistic, effects on responding with conditioned reinforcement. None of the drugs affected the drinking of water in deprived subjects when infused intra-accumbens. These results suggest that both D1 and D2 receptors in the nucleus accumbens are involved in mediating the effects of dopamine in potentiating the control over behaviour by conditioned reinforcers.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Pituitary-adrenal axis responses to acute amphetamine in the rat.

After acute administration of amphetamine (AMPH), a characteristic behavioral response occurs in the rat, involving increased locomotion and stereotyped licking, grooming, and biting. AMPH administration also activates several neuroendocrine systems, including the pituitary-adrenal axis. Because recent evidence has supported a role for glucocorticoids in modulating the behavioral response to AMPH, the purpose of the present study was to examine the relationship between behavioral and hypothalamic-pituitary-adrenal (HPA) responses to AMPH and determine the physiological substrates responsible for the AMPH-induced release of adrenal steroids. AMPH administration produced the often-reported "inverted-U" shaped behavioral response. Specifically, locomotion was increased by low doses (0.5-1.0 mg/kg, SC) significantly more so than by the highest dose (5.0 mg/kg, SC), which instead elicited intense focused stereotyped movements. Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone were increased by AMPH in a monotonic dose-response function, with highest levels measured in rats exhibiting the most intense stereotyped behaviors. Plasma ACTH levels then declined 10-30 min after AMPH administration, while AMPH-induced locomotion and stereotyped behavior persisted well beyond this period. In a parallel study, AMPH failed to elevate plasma levels of vasopressin, an important ACTH secretagogue, and AMPH reduced levels of corticotropin-releasing factor (CRF) immunoreactivity in the median eminence, providing indirect evidence of CRF release from this region. AMPH-stimulated ACTH and corticosterone release were prevented by immunoneutralization of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Modulation of the locomotor response to amphetamine by corticosterone.

In the present experiments, we investigated the influence of chronic modifications of circulating levels of corticosterone on the locomotor response to amphetamine. Different groups of rats were adrenalectomized and implanted subcutaneously with pellets releasing different amounts of corticosterone (0-200 mg). A wide range of corticosterone concentrations was reached in order to saturate selectively either the type I (mineralocorticoid) or the type II (glucocorticoid) corticosteroid receptors. The locomotor response to d-amphetamine (1.5 mg/kg) was studied 10-14 days later. We found that adrenalectomy reduced the response to d-amphetamine by 33% and that a normal response was restored with pellets releasing physiological concentrations of corticosterone (50-mg pellets), and was potentiated in animals with pellets releasing high amounts of corticosterone mimicking chronic stress situations (200-mg pellets). The correlation between plasma corticosterone concentration, locomotor activity following d-amphetamine and thymus weight, which is a reliable indicator of glucocorticoid action, shows that the influence of the locomotor response to d-amphetamine administration is likely to be mediated via a type II receptor. Since the locomotor activating effect of peripheral administration of d-amphetamine has been shown to depend on the integrity of the dopaminergic innervation of the nucleus accumbens, the effect of d-amphetamine at different doses (0, 1, 3, 10 micrograms/microliter) injected directly into the nucleus accumbens was studied. The results demonstrated that removing the circulating corticosterone induced a similar decrease of the locomotor activity elicited by d-amphetamine injection in the nucleus accumbens. This response was restored in animals with the 50- and 200-mg pellets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1992

Corticotropin-releasing factor induces a place aversion independent of its neuroendocrine role.

The purpose of the present experiment was to test the hypothesis that corticotropin-releasing factor (CRF), a polypeptide of 41 amino acids, when administered either intracerebroventricularly (i.c.v.) or subcutaneously (s.c.), has aversive properties in the conditioned place-preference paradigm. Five doses of CRF (0, 0.005, 0.05, 0.5, 5 micrograms) were tested. i.c.v. CRF induced a specific dose-dependent reduction of the amount of time spent in the environment previously paired with the administration of CRF. Furthermore, this CRF-induced place aversion was prevented by pretreatment with alpha-helical-CRF(9-41), a specific CRF antagonist, administered i.c.v. In order to test whether the aversive effects induced by i.c.v. CRF could result from the stimulation of the HPA axis accompanying i.c.v. CRF injection, the reinforcing properties of s.c. CRF were studied using the same dose range. Only the higher s.c. dose was effective in producing a place aversion suggesting that the aversive effects of CRF could not be due solely to the stimulation of the pituitary-adrenocortical system, measured by plasmatic levels of adrenocorticotropic hormone (ACTH) and corticosterone, because the lower doses consistently activate the pituitary-adrenocortical system without producing any behavioral changes. Altogether, these data indicate that the non-neurosecretory CRF neurons may mediate the aversive state occurring during stress.

Animals↗
PubMed1991

Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens.

Three experiments examined the behavioural, pharmacological and neural specificity of the previously reported potentiation of responding with conditioned reinforcement following intra-accumbens d-amphetamine, by studying the effects of intra-accumbens dopamine (DA) and noradrenaline, using an acquisition of a new response procedure. In experiment 1, the effects of intra-cerebral DA infusions (5, 20, 50 micrograms/2 microliters) were compared in four conditions: (i) intra-accumbens DA following positive pairing of the conditioned stimulus (CS) and water during training; (ii) as (i) but also following a systemic dose of the DA receptor antagonist alpha-flupenthixol; (iii) intra-accumbens DA following random pairing of the CS and water during training; and (iv) as (i) but with intra-caudate rather than intra-accumbens DA. The results showed that only with intra-accumbens DA in the positive pairing condition was there a significant dose-dependent increase in responding. In experiment 2, the effects of a higher range of doses (20, 100, 200 micrograms) and smaller infusion volume (5, 25, 50 micrograms/l microliters) of intra-accumbens DA were studied, in comparison with a similar range of doses (5, 25, 50 micrograms/l microliters) of intra-accumbens noradrenaline (NA). Only DA produced a selective, dose-dependent increase in responding with conditioned reinforcement. In experiment 3 neurotoxic lesions of the dorsal noradrenergic bundle (DNAB) using 6-hydroxydopamine producing profound (about 90%) depletion of cortical and nucleus accumbens NA levels had no effect on the increased responding with conditioned reinforcement produced by intra-accumbens d-amphetamine (3, 10, 30 micrograms/l microliters).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Central administration of a CRF antagonist blocks the development of stress-induced behavioral sensitization.

This experiment examined the effects of intracerebroventricular (i.c.v.) administration of a corticotropin-releasing factor (CRF) antagonist on the development of stress-induced sensitization of the behavioral response to amphetamine. Restraint stress was found to enhance both the locomotor response to a s.c. injection of saline and the intensity of stereotypy induced by a s.c. injection of 3.0 mg/kg D-amphetamine. Both of these effects of restraint stress were severely attenuated in rats that had been injected with the CRF antagonist prior to restraint stress. This result is compatible with the hypothesis that CRF is critically involved in initiating behavioral and physiological responses to aversive stimuli.

Amphetamines↗
PubMed1990

Critical role of the hypothalamic pituitary adrenal axis in amphetamine-induced sensitization of behavior.

Behavioral sensitization can be observed with repeated administration of amphetamine where the intensity of motor stimulation increases over time. The process of sensitization has been well characterized, however, the neurochemical mechanisms that are critical for the development of sensitization are not known. In the present study, the role of the hypothalamic pituitary adrenal axis (HPA) in the development of behavioral sensitization to amphetamine was explored by pretreating rats with an intravenous administration of an antiserum to corticotropin-releasing factor in a volume that has been shown to block significantly stress- and cocaine-induced activation of the HPA. Four groups of eight rats were pretreated intravenously with either heparinized saline or CRF antiserum and subcutaneously with saline or d-amphetamine in a balanced design. The rats were then returned to their home cages and left undisturbed for seven days after which they were given three consecutive behavioral tests with saline SC, 0.75 mg/kg d-amphetamine SC, and 3.0 mg/kg d-amphetamine SC. The rats pretreated with intravenous CRF antiserum showed a significant attenuation of the development of d-amphetamine-induced sensitization but the antiserum did not alter the magnitude of the behavioral response to the initial, sensitizing dose of d-amphetamine. These results suggest that activation of the hypothalamic pituitary adrenal axis may be of critical importance to the development of behavioral sensitization to amphetamine.

Animals↗
PubMed1989

Substance P, neurotensin and enkephalin injections into the ventral tegmental area: comparative study on dopamine turnover in several forebrain structures.

A comparison of dopaminergic (DAergic) turnover changes in several forebrain structures was investigated after local injection of substance P (SP), neurotensin and D-Ala-Met-enkephalin (DALA) into the ventral tegmental area (VTA). A dose-dependent increase in the DOPAC/DA ratio was elicited by all 3 peptides in the nucleus accumbens and the septum. DAergic turnover was enhanced in the anteromedial prefrontal cortex only after SP injection and in the amygdala only after neurotensin injection. In the anteromedial striatum as well as in the posterolateral striatum, a significant increased DOPAC/DA ratio was observed following SP and DALA injection into the VTA. No significant changes were noticed in the olfactory tubercles after injection of the 3 peptides in the VTA. From these results, it appears that each peptide induced a different profile of DAergic activation. Taking into account the facilitatory role of the DA neurons at the level of the forebrain integrative structures, the differential activation may explain the difference in behavioral response obtained after injection of the 3 peptides in the VTA.

Animals↗
PubMed1989

Neurotensin, substance P, neurokinin-alpha, and enkephalin: injection into ventral tegmental area in the rat produces differential effects on operant responding.

The neuropeptides neurotensin, substance P, neurokinin-alpha (substance K), and met-enkephalin are present endogenously in the ventral tegmental area (VTA), site of the A10 dopaminergic (DA) cell bodies. In the present study these four peptides were injected bilaterally into the VTA in the rat, and the effects on operant behavior were assessed. Cannulae aimed at the VTA were implanted in four groups of animals, which had been trained to bar-press for food reward on a fixed-interval, 40-s schedule. A fifth group, in which the effects of systemically administered amphetamine were assessed, was also tested. Response rate across the interval was measured, and the index of quarter-life was taken as an indication of the temporal pattern of responding. In addition, a rate-dependency analysis was carried out for all data. Neurotensin (NT, 0.0175, 0.175, 0.5 micrograms in 1 microliter) dose-dependently decreased response rates without affecting quarter-life, and reduced the number of reinforcements obtained. Substance P (SP, 0.1, 1.0, 3.0 micrograms) did not affect responding, and neurokinin-alpha (NKA, 0.1, 1.0, 3.0 micrograms) induced a small increase in responding. Quarter-life was not affected by SP or NKA, but responding on the non-reinforced lever was significantly increased by both peptides. d-Ala-met-enkephalin (DALA, 0.01, 0.1, 1.0 micrograms) induced a dose-dependent increase in responding which was also rate-dependent, and reduced quarter-life. DALA effects were similar to the classic pattern of responding observed after systemic amphetamine. These results suggest that although all these peptides elicit behavioral activation and may affect DA neuronal activity, the behavioral responses can be differentiated with respect to operant behavior.

Animals↗
PubMed1989

Interactions between the amygdala and ventral striatum in stimulus-reward associations: studies using a second-order schedule of sexual reinforcement.

Bilateral, N-methyl-D-aspartate-induced lesions of the basolateral region of the amygdaloid complex in male rats resulted in a marked decrease in instrumental responses maintained by a visual conditioned reinforcer in a paradigm in which sexual reinforcement was presented under a second-order schedule. There were no effects of lesions of the amygdala on the unconditioned sexual behaviour of the males, i.e. on behaviour elicited by primary reinforcers. Infusion of D-amphetamine bilaterally into the nucleus accumbens region of the ventral striatum resulted in a dose-dependent amelioration of the decrease in instrumental behaviour maintained by a conditioned reinforcer which followed lesions of the amygdala. This effect of D-amphetamine critically depended upon the presentation of the conditioned reinforcer (a previously neutral light which had gained reinforcing properties through its prior association with sexual interaction). The results indicate that the basolateral region of the amygdala may interact with dopamine-dependent processes in the ventral striatum in mediating the control by conditioned reinforcers over instrumental behaviour.

Amphetamines↗
PubMed1989

Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum.

The involvement of the amygdala in the potentiation of responding for conditioned reinforcers following intra-accumbens amphetamine injections has been studied. Thirsty rats were trained to associate a light-noise compound stimulus with water and then implanted with guide cannulae in the nucleus accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by accumbens. Half of these rats received excitotoxic lesions of the basolateral region of the amygdala by infusing N-methyl-D-aspartate, whereas the other half received infusions of the vehicle. In the test phase, water was no longer presented but responding on one of two novel levers produced the light-noise compound (the conditioned reinforcer) whereas responding on the other lever had no effect. The two groups received four counterbalanced intra-accumbens infusions of amphetamine (3, 10 and 30 micrograms /microliter) or vehicle over four test days. Intra-accumbens amphetamine infusions dose-dependently increased responding on the lever providing a conditioned reinforcer but had no significant effect on responding on the lever which did not produce the conditioned reinforcer. Compared with controls, the lesioned group exhibited a significant, selective reduction in responding on the lever providing a conditioned reinforcer, with no change on the lever on which responding had no consequence, irrespective of drug or control treatment. Control experiments showed that the amygdala lesioned animals were not hypodipsic and exhibited similar levels of hyperactivity following intra-accumbens infusions of D-amphetamine. Furthermore, the capacity to discriminate the conditioned stimulus as well as to acquire a new motor task was not altered by the lesion. These results indicate a role for the amygdala in mediating the effects of stimulus-reward associations on behaviour, via an action on dopamine-dependent mechanisms of the ventral striatum.

Amphetamines↗
PubMed1988

d-Ala-met-enkephalin injection into the ventral tegmental area: effect on investigatory and spontaneous motor behaviour in the rat.

The mesolimbic dopamine (DA) system, originating in the ventral tegmental area and projecting to limbic forebrain regions, plays a crucial role in mediating several important aspects of behaviour. Proximal to these DA neurons are enkephalin-containing nerve fibers. In an attempt to characterize the behavioural role of enkephalinergic transmission in the VTA, the present experiment examined in detail the investigatory and motor responses to microinfusion of d-ala-met-enkephalin (DALA), a long lasting analogue of enkephalin, into the ventral tegmental area (VTA). Injections into the substantia nigra (SN) and the hippocampus (HPC) were also performed as controls for site specificity. The behavioural apparatus consisted of an eight-hole box monitored by a video camera. Four doses of DALA were injected in the VTA (0.05, 0.1, 1 and 2.5 micrograms/microliters bilaterally in 1 microliter volume) and one dose in the SN and HPC (0.1 microgram/microliter bilaterally in 1 microliter volume). The effect of DALA injections in the VTA was characterized by an inverted U-shape dose-effect curve. The low doses (0.05 and 0.1) induced an increase in the frequency of hole visits accompanied by a decrease in the mean duration of visits, whereas the highest doses induced a decrease in hole visit frequency. Low doses of DALA had no effect on strategy or organization of exploration, whereas the high doses produced decreased switching between holes. After low doses of DALA, locomotor activity at the periphery of the testing box was not significantly affected but locomotor activity in the centre was increased. After high doses of DALA, locomotor activity in the center and at the periphery of the box were decreased. Frequency of rearing was either not affected or decreased by DALA treatment. DALA injected in the SN resulted in a small increase in frequency of hole visits and did not affect rearing and locomotor activity. DALA injection in the HPC had no effect on investigatory and spontaneous motor behaviour. The results are discussed in terms of a modulatory role of endogenous enkephalin on mesolimbic dopamine neurons.

Animals↗
PubMed1986

Ventral tegmental area infusion of substance P, neurotensin and enkephalin: differential effects on feeding behavior.

The neuropeptides substance P, neurotensin and [Met]enkephalin are found in the ventral tegmental area, site of the A10 dopamine cell bodies. Evidence suggests a functional interaction between these peptides and the dopaminergic neurons. All three peptides have been shown to exert an activating effect on these neurons. The present study analyzed the effects of ventral tegmental area infusion of neurotensin, substance P and D-ala-[Met]enkephalin on feeding behavior. These effects were studied in both food-deprived and satiated rats. During a 30 min test, the following parameters were registered: latency to eat, total food intake, food spillage, number of eating bouts and duration of eating. Similar measures were taken for drinking. In deprived rats substance P (0.5, 3.0 micrograms) increased latency to eat but did not affect other parameters, and substance P did not affect eating in satiated rats. Neurotensin (0.5, 2.5 micrograms) increased latency to eat and markedly reduced food consumption in deprived rats and had no effect in satiated rats. D-Ala-[Met]enkephalin (0.1, 1.0 micrograms) stimulated feeding behavior in both deprived and satiated rats. These results show that although the different peptides are presumed to activate the dopaminergic A10 neurons, their effects on feeding behavior can be differentiated. The findings are discussed in terms of motor and motivational mechanisms, and the relative contributions of specific and non-specific influences on feeding are considered.

Animals↗