Biomedical subjects

C Spyraki

Publications and source records attributed to C Spyraki.

At least 19 recordsLinked to original sources

PubMed1995

Ventral pallidum self-stimulation: a moveable electrode mapping study.

The distribution of electrical self-stimulation (ESS) foci within the ventral pallidum (VP) was mapped using moveable electrodes in rats. The function relating ESS bar-pressing rate to the frequency of cathodal rectangular pulses (0.4 mA and 0.1 ms) was obtained for several positions of a moveable electrode in the VP and in the various adjacent to VP nuclei. The rate-frequency functions were fitted to a sigmoid model to obtain the asymptotic rate and threshold frequency. ESS was found in almost all (98%) VP sites tested and to a lesser degree (66%) in the surrounding areas (namely globus pallidus and caudate). Depending on the VP site, maximum rates varied from 14 to 85 bar presses/min, whereas threshold frequencies varied from 10.2 to 36.4 pulses/train; no correlation between these two aspects of ESS was found. Extra-pallidal areas contained less low-frequency threshold sites compared to VP. The lowest threshold found in the VP was slightly higher than that usually obtained for the most rewarding brain areas (VTA, dorsal raphé, LH, amygdala), which suggests that the VP represents an important structure for reward. Furthermore the threshold frequencies were found to decline along the rostrocaudal axis of the VP which supports the view that the VP is heterogeneous in regard to reward related functions.

Amygdala↗

PubMed1995

Poststimulation excitability of ventral pallidum self-stimulation neurons.

The degree of neural recovery from refractoriness was inferred in rats self-stimulating with pairs of pulses in the ventral pallidum. The prerecovery intrapair interval varied from 0.5 to 1.0 ms, depending on brain site. At some sites, recovery reached its maximum within less than 1.6 ms whereas, at the majority of sites, a substantial amount of recovery occurred at delays longer than 1.2 ms. The shortest recovery estimates were not fundamentally different from those obtained from sites lying along the medial forebrain bundle. The longest recovery estimates were similar to those obtained from cortical and basal forebrain sites. The differences in recovery noted between sites and the presence of step-like patterns in the recovery curves suggest the presence of neural heterogeneity within the ventral pallidal substrates of reward.

Animals↗

PubMed1994

Effect of morphine applied by intrapallidal microdialysis on the release of dopamine in the nucleus accumbens.

The effect of morphine, administered intrapallidally, on extracellular concentrations of DA, DOPAC, and HVA in the nucleus accumbens and striatum was studied in the behaving rat using the in vivo microdialysis technique. Unilateral application of morphine hydrochloride was performed through microdialysis probes into the rat ventral pallidum (10 microliters of 0, 2.6, 4.0, 13.0, and 26.0 mM) or globus pallidus (10 microliters of 0 and 26.0 mM). The levels of DA, DOPAC, and HVA were measured using the HPLC with EC detection in dialysates collected from the nucleus accumbens, anteromedial, and anterolateral striatum. Samples were taken every 45 min over 3 h before and over 5 h after morphine or vehicle administration. Administration of morphine into the ventral pallidum resulted in increased DOPAC and HVA concentrations in the nucleus accumbens. Pretreatment with naloxone (1 mg/kg, SC) abolished this effect of morphine. Administration of morphine into the globus pallidus resulted in increased DA, DOPAC, and HVA concentrations in the nucleus accumbens and DA in the anteromedial striatum. The levels of DA and metabolites in anterolateral striatum remained rather unchanged following morphine administered into the ventral pallidum or the globus pallidus. The changes in DA neurotransmission into the nucleus accumbens induced by morphine application into the ventral pallidum and globus pallidus are reminiscent of a phasic and tonic release of DA respectively. The results show that intrapallidal morphine increases DA neurotransmission in nucleus accumbens and suggest that the effect of morphine is mediated by ventral pallidum/mesolimbic and globus pallidus/thalamocortical pathways, depending on the site of injection.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Regulation of dopamine D2 receptor mRNA expression in the olfactory tubercle by cocaine.

The influence of acute and chronic cocaine treatment on the expression of dopamine D2 receptor (D2R) mRNA was examined in the rat basal ganglia by in situ hybridization histochemistry. No significant alterations in D2R mRNA levels were observed in the striatum or the nucleus accumbens following acute or chronic cocaine. In the olfactory tubercle, acute cocaine (20 and 40 mg/kg, i.p.) was found to decrease D2R mRNA expression. Chronic cocaine (20 mg/kg, i.p. x 15 days), however, produced an increase in D2R mRNA levels in this region which was detected 24 h, but not 7 days after withdrawal. Acute and chronic cocaine have different effects on the regulation of D2R gene expression in the olfactory tubercle.

Animals↗

PubMed1993

Neuronal release of somatostatin in the rat striatum: an in vivo microdialysis study.

Extracellular levels of somatostatin in the rat striatum were studied using in vivo microdialysis and radioimmunoassay. In vitro studies were performed using three different dialysis membranes at various flow rates and temperatures to assess the optimal recovery of somatostatin. The best results were obtained when a cellulose fibre membrane was utilized at 37 degrees C with a flow rate of 0.5 microliters/min. For the in vivo studies, transcerebral cellulose probes were implanted in the striatum of chloryl hydrate-anaesthetized rats. Basal levels of somatostatin were detected in the striatum of the freely moving animals and found to be 5-15 fmol. Stimulation with 100 mM KCl increased the recovered somatostatin by 138% (P < 0.05). A second stimulation following a 3-h interval increased the somatostatin levels by approximately 60%. The addition of veratridine (100 microM) in the perfusion medium increased the somatostatin levels recovered from the striatum by 85% (P < 0.01). Following a 3-h interval, a second stimulation by veratridine also increased somatostatin levels (43%). The increases observed after the second depolarizing stimulus (KCl and veratridine) were not found to be significantly different from basal levels. Both EGTA and the sodium channel blocker tetrodotoxin attenuated the effect of KCl and veratridine, respectively. However, neither EGTA nor tetrodotoxin had an effect on the basal levels of somatostatin recovered. These results indicate that (i) the somatostatin measured is neuronally released in the striatum and (ii) microdialysis is a useful tool for examining the regulation of somatostatin release in the brain.

Analysis of Variance↗

PubMed1992

Analgesia induced by morphine injected into the pallidum.

Bilateral microinjections of morphine hydrochloride (10; 20; 30 micrograms/0.5 microliter/side) or saline were aimed at three different regions of the rat globus pallidus: dorsal, medial, ventral. Before and at various intervals after intrapallidal morphine (15; 30; 60; 90; 180 min), estimation of pain threshold was made by the hot plate procedure. Dose-dependent morphine analgesia was elicited from all three regions injected. Differences between the pallidal areas as to the intensity and duration of the drug's effect were noticed. Pretreatment with subcutaneous naloxone (1 mg/kg, s.c.) inhibited the morphine (20 micrograms) analgesia elicited from the medial and dorsal pallidum; it decreased and delayed the effect of morphine injected into the ventral pallidum. The results suggest that the three pallidal areas tested are involved to a different degree (medial/dorsal greater than ventral) in the morphine analgesia mediated by opiate receptors.

Animals↗

PubMed1992

Effects of acute and chronic desipramine treatment on somatostatin receptors in brain.

The effects of acute (5 mg/kg, IP twice daily for 2 days) and chronic (5 mg/kg IP twice daily for 21 days) administration of desipramine (DMI) on [125I]-Tyr11-somatostatin binding sites in brain were examined. There was no change in [125I]Tyr11-somatostatin binding in membranes prepared from the frontal cortex, striatum, and hippocampus of rats acutely or chronically treated with DMI as compared to non treated animals. [125I]Tyr11-somatostatin binding was increased in membranes prepared from the rat nucleus accumbens only after chronic DMI administration. Scatchard analysis of the binding data from the nucleus accumbens showed that [125I]Tyr11-somatostatin labels a single population of somatostatin binding sites with an affinity constant, Kd, of 1.8 +/- 0.60 nM and a Bmax of 330 +/- 90 fmol/mg protein. Chronic treatment with DMI increased the Bmax (500 +/- 140 fmol/mg protein) but had no effect on the Kd. This finding shows a regional effect of DMI on [125I]Tyr11-somatostatin binding sites in rat brain and suggests that somatostatin may play a role in the pathophysiology of depression.

Animals↗

PubMed1992

Pallidal substrate of morphine-induced locomotion.

Bilateral microinjections of morphine hydrochloride (5.0; 7.5; 10.0 micrograms/0.5 microliters/side) or saline were infused into 3 different regions (dorsal, medial, ventral) of the rat globus pallidus, to examine their effects on locomotor activity. Locomotor activity of each rat was measured 45 min before and 90 min after saline or morphine pallidal microinjections. Morphine induced a dose-dependent increase in locomotion. This increase in locomotion was also significantly different between the 3 pallidal regions. Pretreatment with naloxone (1 mg/kg, sc) inhibited the morphine (7.5 micrograms) hyperlocomotion elicited from all three pallidal areas. The results suggest that the entire pallidum serves as substrate of morphine hyperlocomotion mediated by opiate receptors.

Animals↗

PubMed1988

Cocaine-induced place conditioning: importance of route of administration and other procedural variables.

It has been shown that pretreatment with dopamine (DA) receptor blockers disrupts the effect of intravenously (IV) and intracerebrally (ICV), but not intraperitoneally (IP) administered cocaine on place preference conditioning (PPC). The present study was undertaken to further evaluate possible differences between IV and IP cocaine PPC. To this end, several factors which may differentially influence IV and IP cocaine PPC were examined. Firstly, dose-response effects were studied. Intravenous cocaine produced PPC within a narrow dose range (0.5-2.5 mg/kg). Animals receiving IV injections of 5 and 10 mg/kg cocaine experienced convulsions and did not show PPC. For IP cocaine a 10-fold increase in dose (10 mg/kg) and twice the number of training trials was required in order to obtain PPC equal in magnitude to that with IV cocaine (0.5 mg/kg; two trials). Cocaine PPC was retained at least 1 month. Following IV cocaine preference developed for the side associated with the drug regardless of whether the conditioning was to the least or most preferred side. After IP cocaine, preference developed for the drug side only when the drug was paired with the least preferred side. Rats trained with IV, but not IP, cocaine significantly preferred the drug familiar side to a novel compartment. Preference for the IV or IP cocaine side developed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation of the cocaine PPC. The results show PPC procedure to be a valid test for evaluating rewarding properties of IV cocaine. However, they fail to show rewarding effects of IP cocaine.

Animals↗

PubMed1988

A role for the mesolimbic dopamine system in the reinforcing properties of diazepam.

The conditioned place preference paradigm was used to investigate the neurochemical and neuroanatomical substrates which mediate the rewarding properties of diazepam. The results confirmed that diazepam (1 and 2.5 mg/kg, IP) produced place preference for a distinctive environment that had previously been paired with injections of the drug. Pretreatment with haloperidol (0.1 mg/kg) antagonised the place preference induced by diazepam (1 mg/kg). Pretreatment with domperidone (2 mg/kg) failed to influence this effect of diazepam. Haloperidol (0.1 mg/kg) and domperidone (2 mg/kg) alone did not produce place aversion. In separate experiments the diazepam-induced place preference was examined in rats having 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. These animals did not show preference for the compartment associated with diazepam. Depletion of central noradrenaline produced by systemic injections of DSP4 did not affect diazepam-induced place preference conditioning. These findings suggest that dopamine-containing neurons of the mesolimbic system are a component of the neural circuitry that mediates the reinforcing properties of diazepam.

Animals↗

PubMed1988

Influence of oestrogen on spontaneous and diazepam-induced exploration of rats in an elevated plus maze.

An elevated plus-maze, used to identify anxiolytic effects of drugs (Pellow et al., 1985), reflected as increased open-arm exploration, was employed in cycling and ovariectomised rats, to determine the effect of diazepam on the cycle and, after ovariectomy, to investigate possible influences of treatment with oestradiol (10 or 100 micrograms/kg, s.c.) (acute: 1 day or subchronic: 3 days) to ovariectomised rats on the effect of diazepam (1 mg/kg, i.p.), studied 3, 24 and 72 hr after cessation of treatment. Cycling females, exhibiting 3 consecutive 4-day oestrous cycles and ovariectomised rats, 15 days after surgery, were used. There was a tendency for increased open-arm exploration by rats in proestrous and diestrous, as compared to the other phases of the cycle and to ovariectomised rats. Rats treated 24 hr after subchronic treatment with oestradiol also exhibited increased open-arm exploration. The anti-anxiety effect of diazepam was clearly shown in oestrous and metestrous but not in proestrous, diestrous or in ovariectomised rats. The effect of diazepam was abolished in rats tested 3 hr after acute small doses of estradiol and attenuated in rats tested 24 hr after subchronic administration of the hormone. The results suggest that oestradiol, administered in physiological doses, may have an inhibitory effect on the diazepam-induced anxiolysis.

Animals↗

PubMed1988

Behavioural and biochemical effects of haloperidol during the oestrous cycle of the rat.

The effects of two doses (1 and 2 mg/kg, i.p.) of haloperidol (HAL) on catalepsy, on concentrations of DA and DOPAC in frontal cortex, nucleus accumbens and striatum and on serum levels of oestradiol were investigated in intact female rats during the 4-day oestrous cycle. Catalepsy induced by haloperidol did not vary much during phases of the cycle. The turnover of DA in the cortex induced by haloperidol was significantly greater on proestrus and smaller on oestrus. The effect of haloperidol on the turnover of DA in the nucleus accumbens and in striatum was marginally affected by the oestrous cycle being greatest on oestrus. The levels of serum oestradiol were higher on proestrus and lower on oestrus. No significant differences were detected between diestrus and metestrus. After haloperidol there was a dramatic increase in serum oestradiol on oestrus, a slight increase on metestrus and diestrus and a decrease on proestrus. However, serum levels of oestradiol were not significantly different between phases of the cycle in rats treated with haloperidol. The results indicate that the oestrous cycle has a detectable influence on DAergic mechanisms in the frontal cortex and possibly in the tuberoinfudibular system, brought about by treatment with haloperidol.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Effects of ritanserin on the rewarding properties of d-amphetamine, morphine and diazepam revealed by conditioned place preference in rats.

The possibility that 5-HT2 receptors mediate the reinforcing properties of d-amphetamine, morphine and diazepam was investigated in rats, using ritanserin, a 5-HT2 antagonist, and the conditioned place preference paradigm. Ritanserin 1 or 2.5 mg/kg did not cause place conditioning. Place preference induced by 1.5 mg/kg d-amphetamine and 2 mg/kg morphine was inhibited and attenuated respectively by pretreatment with 2.5 mg/kg ritanserin. Diazepam- (1 mg/kg) induced place preference was completely blocked by both doses of ritanserin. Ritanserin pretreatment failed to influence amphetamine-induced hyperlocomotion, morphine-induced analgesia and diazepam-induced increased open arm exploration of rats on the elevated plus maze. These data are discussed in terms of (a) the possibility that serotoninergic mechanisms have a role in mediating reinforcement and (b) the relationship between appetitive properties and specific behavioral effects of psychostimulants, opiates and anxiolytics.

Analgesia↗

PubMed1988

Drug-induced place preference in rats with 5,7-dihydroxytryptamine lesions of the nucleus accumbens.

The conditioned place preference (CPP) paradigm was used to determine a role for serotonin in the nucleus accumbens in the mediation of the rewarding properties of D-amphetamine morphine and diazepam. The effect of these drugs on CPP was examined in controls and in animals with 5,7-dihydroxytryptamine lesions of the nucleus accumbans. The results from control animals confirmed that D-amphetamine (1.5 mg/kg, i.p.), morphine (2.0 mg/kg, i.p.) and diazepam (1.0 mg/kg, i.p.) produced place preference for a distinctive environment that had previously been paired with injections of the drug. In animals with 80% reduction of 5-hydroxytryptamine content of the nucleus accumbens, D-amphetamine CPP was unchanged and morphine CPP was attenuated compared with controls. Diazepam CPP was not apparent in animals with the lesion. In separate experiments, characteristic behavioural effects of the drugs under study were examined in control and in animals with lesion. The results showed a tendency for increased amphetamine hyperlocomotion, enhanced morphine activity and analgesia and decreased diazepam anti-anxiety effect in animals with lesions. Thus, the 5,7-dihydroxytryptamine lesions of the nucleus accumbens differently influenced the CPP induced by the drugs studied and, with the exception of diazepam, the various behavioural effects elicited by each drug. The findings suggest that serotonin-containing neurones of the nucleus accumbens are a component of the neural circuitry that mediates the rewarding properties of morphine, probably of diazepam, but not of D-amphetamine.

5,7-Dihydroxytryptamine↗

PubMed1988

Chronic antidepressant treatment increases the apomorphine-induced elevation of plasma corticosterone in rats.

Plasma corticosterone concentrations in response to subcutaneous administration of apomorphine (25 and 200 micrograms kg-1) have been assessed in rats treated acutely (2 days) or repeatedly (15 days) with saline, clomipramine, electroshock and clomipramine + electroshock. Chronic, but not acute, antidepressant treatment decreased the corticosterone level which remained unchanged in control and in rats acutely treated with apomorphine. Chronic antidepressant treatment significantly increased the corticosterone response to apomorphine. Neuroendocrine evidence is provided for an increased responsiveness of dopamine receptors which are thought to mediate the apomorphine effect on corticosterone secretion following chronic antidepressant treatment.

Animals↗

PubMed1987

Apomorphine-induced behaviour during the oestrous cycle of the rat.

The effect of various doses of apomorphine (APO) (25, 250, 400 and 750 micrograms/kg, s.c.) on open field behaviour, stereotyped behaviour, body temperature and concentrations of serum oestradiol was studied in cycling females and in ovariectomized rats. With the exception of grooming, the hormonal variations during the cycle, or the ovariectomy, did not have an effect on behaviour related to stimulation of presynaptic dopamine (DA) receptors. The endocrine status on proestrus (PE), characterized by an increase in serum oestradiol, did influence hyperlocomotion and hypothermia induced by apomorphine; the former being attenuated and the latter increased, as compared to the other phases of the cycle. Ovariectomy resulted in an increase in the stimulatory effect of apomorphine on locomotion. Stereotypy induced by apomorphine was unaltered by hormonal variations during the cycle and it was slightly attenuated by removal of the ovaries. During phases of low levels of oestrogen (oestrus, metestrus) apomorphine significantly increased the levels of serum oestradiol, determined 30 min after the administration of drug. It is concluded that the various DAergic mechanisms in brain are differentially affected by hormonal variations during the cycle and by ovariectomy.

Animals↗

PubMed1987

Estrogen treatment to ovariectomized rats modifies morphine-induced behavior.

Two weeks after surgery, ovariectomized (OVX) rats were treated for 3 days with either 17 beta-estradiol (10 or 100 micrograms/kg, SC, per day) or the oil vehicle. They were then tested for morphine-induced hyperactivity (4 mg/kg, IP), analgesia and catalepsy (15 and 20 mg/kg, IP) 24 or 72 hr after the last steroid or oil injection. Estradiol treatment did not affect the locomotion or the sensitivity to nociceptive stimuli of OVX rats and did not induce a cataleptic state in animals. Estradiol- (100 micrograms/kg) treated OVX rats exhibited attenuated morphine-induced hyperlocomotion regardless of the time that had elapsed after estradiol treatment cessation, attenuated morphine-induced catalepsy at 24 hr after estradiol treatment and unaltered morphine-induced analgesia. OVX rats treated with a lower estradiol dose (10 micrograms/kg) exhibited significantly increased morphine-induced analgesia and slightly increased catalepsy. The results show that the sensitivity of brain opiate systems controlling some of the behavioral effects of morphine is modified following estradiol treatment to OVX rats.

Analgesia↗

PubMed1987

Intravenous cocaine-induced place preference: attenuation by haloperidol.

Cocaine reward was demonstrated by establishing a conditioned place preference (CPP) to a distinctive location paired with cocaine administered either intravenously (i.v., 0.5 mg/kg) or intraperitoneally (i.p., 10 mg/kg). Significant i.p. or i.v. cocaine CPP was observed following the second conditioning trial. Haloperidol (0.2 mg/kg) pretreatment disrupted CPP induced by i.v., but not i.p., cocaine. The haloperidol effect built up over successive trials. The involvement of dopaminergic transmission in i.v. cocaine-induced CPP is discussed.

Animals↗