Spiral CT: applications in the emergency patient

The influence of vasopressin (AVP) on recall of information in a passive avoidance situation after bilateral 6-OHDA lesions to the central amygdala was tested. AVP given 15 min before the retention testing at the icv dose of 1 microgram significantly prolonged avoidance latencies both in lesioned and in sham-operated rats in comparison with the respective icv saline injected animals. Insignificant increase of spontaneous locomotor activity in rats lesioned to the central amygdala was unlikely to interfere with the cognitive effect of AVP. These results suggest that dopaminergic projection to the central amygdala is not responsible for the facilitatory effect of AVP on retrieval process in a passive avoidance situation.     

Electrical stimulation of the prefrontal cortex increases cholecystokinin, glutamate, and dopamine release in the nucleus accumbens: an in vivo microdialysis study in freely moving rats

In vivo microdialysis, radioimmunoassay, and HPLC with electrochemical or fluorometric detection were used to investigate the release of cholecystokinin (CCK), glutamate (Glu), and dopamine (DA) in nucleus accumbens septi (NAS) as a function of ipsilateral electrical stimulation of medial prefrontal cortex (mPFC). CCK was progressively elevated by mPFC stimulation at 50-200 Hz. Stimulation-induced CCK release was intensity-dependent at 250-700 microA. NAS Glu and DA levels were each elevated by stimulation at 25-400 Hz; the dopamine metabolites DOPAC and homovanillic acid were increased by stimulation at 100-400 Hz. When rats were trained to lever press for mPFC stimulation, the stimulation induced similar elevations of each of the three transmitters to those seen with experimenter-administered stimulation. Perfusion of 1 mM kynurenic acid (Kyn) into either the ventral tegmental area (VTA) or NAS blocked lever pressing for mPFC stimulation. VTA, but not NAS, perfusion of Kyn significantly attenuated the increases in NAS DA levels induced by mPFC stimulation. Kyn did not affect NAS CCK or Glu levels when perfused into either the VTA or NAS. The present results are consistent with histochemical evidence and provide the first in vivo evidence for the existence of a releasable pool of CCK in the NAS originating from the mPFC. Although dopamine is the transmitter most closely linked to reward function, it was CCK that showed frequency-dependent differences in release corresponding most closely to rewarding efficacy of the stimulation. Although not essential for the reward signal itself, coreleased CCK may modulate the impact of the glutamatergic action in this behavior.     

Effects of repeated nicotine pre-treatment on mesoprefrontal dopaminergic and behavioral responses to acute footshock stress

The effects of acute and repeated nicotine administration on the stress response of rat mesoprefrontal dopaminergic pathways were examined. Rats were given daily injections of nicotine (0.15 or 0.60 mg/kg, s.c., freebase) or saline for 4 days, then challenged with either nicotine or saline. A regimen of inescapable electrical footshocks or no footshocks was then administered. Thirty minutes after final injection, rats were sacrificed, brains removed and dopamine (DA) and its metabolite dihydroxy-O-phenylacetic acid (DOPAC) were extracted from medial prefrontal cortex (mPFC), nucleus accumbens septi (NAS) and dorsolateral striatum and quantified by high performance liquid chromatography with electrochemical detection. Acute administration of low dose nicotine (0.15 mg/kg) produced an increase in DA utilization (increased DOPAC/DA ratio) in mPFC and NAS, but not striatum. High dose nicotine (0.60 mg/kg) produced activation in NAS, but not mPFC or striatum. Repeated low dose nicotine pre-treatment produced tolerance to the effects of nicotine challenge in the mPFC, and reduced its effects in NAS. Footshock stress preferentially increased DA utilization in mPFC and associated footshock stress-induced immobility responses, and these were reduced by low, but not high, dose repeated nicotine pre-treatment. Further, a single dose of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (MCA) 30 min prior to nicotine challenge dose-dependently blocked the reduction of mesoprefrontal DA stress responsivity and immobility responses produced by repeated nicotine pre-treatment. These results indicate that: (1) there are dose-dependent differential effects of acute and repeated nicotine pre-exposure on regional DA utilization; (2) low, but not high, dose repeated nicotine reduces both the mesoprefrontal DA and behavioral effects of acute footshock stress; and (3) these effects of repeated nicotine may depend on mecamylamine-sensitive nAChR stimulation. These results may have relevance to acute stress and nicotine dependence, particularly in schizophrenic disorders, which have high prevalence rates of co-morbid nicotine dependence, stress-induced symptom exacerbation and prefrontal cortical dysfunction.     

Neostriatal dopamine and sensory inattention.

Damage to the mesotelencephalic dopamine (DA)-containing projection results in a sensory inattention, characterized by impairments in orientation toward somatosensory, visual, and olfactory stimuli. Experiments with Sprague-Dawley rats investigated which branch of the dopaminergic system is responsible for these deficits. In the 1st approach, DA-innervated forebrain sites were damaged by 6-hydroxydopamine (6-OHDA) injection into, or by electrolytic lesions of, these regions. In the 2nd, Ss were given tegmental 6-OHDA injections that damaged the entire mesotelencephalic projection and subsequently received intracerebral injections of the DA agonist apomorphine into forebrain sites in an attempt to reinstate orientation. Results demonstrate that dopaminergic terminals in the neostriatum are critical for orientation. Unilateral neostriatal 6-OHDA injections or electrolytic lesions reduced orientation to contralateral touch, whereas similar damage to other DA-innervated forebrain structures did not. Results also suggest that dopaminergic terminals in the anterior neostriatum are important for orientation to the touch of the rostral body surface, while those in the posterior neostriatum are most critical for orientation to caudal touch. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of damage to the n. accumbens septi on drinking behavior and on the ion-regulatory and excretory functions of the kidneys

The experiments on adult male rats have shown that electrolytic damage of the n. accumbens septi (NAS) increases the water intake and the kaliuretic response. The NAS damage and intragastric water administration in the quantity 5% to the bodyweight influence on the renal natrium excretion and on the glomerular filtration. The possible mechanisms of influences of the limbic damages on the drinking behaviour and on the renal solute and water excretion are discussed.     

Lesions of the substantia nigra retard Pavlovian eye-blink but not heart rate conditioning in the rabbit.

Bilateral radio-frequency (RF) lesions of the substantia nigra retarded Pavlovian eye-blink (EB) conditioning without affecting concurrent heart rate (HR) conditioning. Dopamine (DA) depletion occurred only in the caudate nucleus, whereas norepinephrine (NE) depletion was limited to the hypothalamus. Bilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra retarded acquisition of both EB and HR responses. Six-OHDA lesions produced significant NE depletion in the nucleus acumbens/septi, frontal cortices, and hypothalamus, as well as DA depletion in the caudate nucleus. Trials required to reach EB conditioning criterion were significantly correlated to the caudate DA levels. The magnitude of conditioned bradycardia was on the other hand significantly correlated with hypothalamic NE levels. Results suggest that interruption of the nigro-striatal dopaminergic pathway retards Pavlovian somatomotor learning without affecting concurrent autonomic learning, although the latter may depend on an intact ascending NE pathway to the hypothalamus, which passes through the tegmentum and thus is also destroyed in some cases by substantia nigra lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral activity of 1S,3R-ACPD, an agonist of metabotropic glutamate receptors

The influence of intracerebroventricular (i.c.v.) injections of 1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), an agonist of metabotropic glutamate receptors, on the activity of the central nervous system was examined in rats. 1S,3R-ACPD at the i.c.v. doses of 100 and 200 nmole significantly decreased apomorphine-induced stereotypy, and at a dose 200 nmole significantly diminished catalepsy caused by haloperidol, two behavioral symptoms controlled mainly by central dopaminergic system. The tested compound had no influence on the locomotor and exploratory activity of rats estimated in open field. 1S,3R-ACPD significantly improved acquisition at the i.c.v. dose of 100 nmole, and consolidation of information at the i.c.v. doses of 100 and 200 nmole. The tested compound had no influence on retention processes in passive avoidance situation. This compound also did not improve recognition memory tested in the object recognition test. These results indicated that 1S,3R-ACPD improved memory motivated affectively but had no influence on recognition memory and the diminished dopaminergic transmission.     

Extensive sequence divergence between the human and rat brain vesicular monoamine transporter: possible molecular basis for species differences in the susceptibility to MPP+

Experiments were performed on 40 adult rabbits immobilized with Flaxedil. The effect of stimulation of amygdaloid complex on the click evoked potential of Woolsey's AI, AII and the auditory cortex behind the rhinal sulcus (ACBRS) was examined by single unit analysis. The results showed that stimulation of lateral nucleus and basal nucleus of amygdala could induce either a facilitory or an inhibitory effect on the evoked potential and the unit discharges. The latency of the inhibitory effect was about 10-25ms, and lasted for 20-115ms. A facilitory effect with a latency as short as 2ms was also observed in one animal. The experimental results indicate that the effect of amygdaloid complex stimulation as transmitted through polysynaptic circuit while the facilitatory effect was monosynaptic. The functional significance of the amygdaloid effect was discussed.     

Neuropeptide FF in the VTA blocks the analgesic effects of both intra-VTA morphine and exposure to stress

Experiments were designed to examine the analgesic effects induced by selective tachykinin receptor agonists microinfused into either the ventral tegmental area (VTA) or nucleus accumbens septi (NAS). Rats were tested in the formalin test for tonic pain following an injection of 0.05 ml of 2.5% formalin into one hind paw immediately after bilateral intra-VTA infusions of either the NK-1 agonist, GR-73632 (0.005, 0.05 or 0.5 nmol/side), the NK-3 agonist, senktide (0.005, 0.5 or 1.5 nmol/side), or saline. Two weeks later, the saline-treated rats were assessed in the tail-flick test for phasic pain after infusions of the tachykinin agonists. Tail-flick latencies were recorded following immersion of the tail in 55 degrees C hot water at 10 min intervals for 1 h immediately after intra-VTA infusions of either GR-73632 (0.5 nmol/side), senktide (1.5 nmol/side) or saline. In a second group of rats, the same effects were studied after infusions into the nucleus accumbens (NAS) of GR-73632 (0.005, 0.5 or 1.5 nmol/side), senktide (0.005, 0.5 or 1.5 nmol/side), or saline. In both the VTA and NAS, the NK-1 and the NK-3 agonists caused significant analgesia in the formalin test, although the NK-1 agonist appeared to be more effective. Naltrexone (2.0 mg/kg) pretreatment failed to reverse the analgesic effects in the formalin test induced by intra-VTA infusions of the substance P (SP) analog, DiMe-C7 (3.0 microg/side), GR-73632 (0.5 nmol/side), or senktide (1.5 nmol/side). Neither compound given at either site was effective in the tail-flick test. These findings suggest that SP-dopamine (DA) interactions within the mesolimbic DA system play an important role in the inhibition of tonic pain. Furthermore, they support our earlier ideas that activation of midbrain DA systems by SP might play a role in stress- and/or pain-induced analgesia.     

Intrastriatal infusion of lisuride--a potential treatment for Parkinson's disease? Behavioral and autoradiographic studies in 6-OHDA lesioned rats

The present study examined the effect of chronic intrastriatal infusion of the dopamine receptor agonist lisuride on apomorphine-induced rotational behaviour and on D2-dopamine receptors in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. The completeness of the lesion of the right ascending nigrostriatal dopaminergic pathway was confirmed by apomorphine-induced rotation and [3H]-mazindol autoradiography. The intrastriatal infusion of lisuride (0.5 microgram/h) into the lesioned striatum for 2 weeks induced an immediate but temporary spontaneous contralateral rotation and a reduction of apomorphine-induced rotation of 47.2% relative to pre-lisuride infusion. The density of D2-receptors in the lisuride-infused striatum was significantly decreased by 40% relative to vehicle-infused 6-OHDA lesioned rats. The level of D2-dopamine receptors returned to normal levels 3 weeks after the termination of lisuride infusion. These results show that the intrastriatal infusion of lisuride reverses the behavioural and D2-dopamine receptor changes present in the 6-OHDA lesion rat model of Parkinson's disease.     

Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat.

In Exp I with 24 male albino Wistar rats, bilateral 6-hydroxydopamine lesions of the nucleus accumbens septi (NAS) and olfactory tubercle (OT) caused enhanced intake of wet mash in 23-hr-food-deprived Ss tested in photocell activity cages during restricted 30-min sessions. This mild hyperphagia was accompanied by a significant hypoactivity in the group with NAS/OT lesions. No hyperphagia was observed during a prolonged 120-min test session or in free-feeding tests conducted in the home cage. Anorexia induced by dextroamphetamine (.5 and 1.5 mg/kg) was unaltered by the lesion, although the locomotor stimulant action of the drug was attenuated. Results of Exp II, with 36 Ss, show that the NAS/OT lesion also enhanced food intake in the photocell cages during 30-min sessions with dry food pellets but that food-associated drinking was concomitantly reduced. Results are consistent with the hypothesis that the behavioral changes caused by mesolimbic neuron destruction result in part from an inability to switch from one behavioral activity to another. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Angiotensin III-induced dipsogenic and pressor responses in rodents.

Three experiments examined responses to angiotensins in 64 male Sprague-Dawley rats, 64 male Mongolian gerbils, and 40 Octodon degus—a South American rodent. In Exp I, injections of [des-Asp–1]-angiotensin I ([des-Asp–1]-AI), angiotensin II (AII), and angiotensin III (AIII), at doses of .001–2 mg/kg (sc), induced drinking in the rat and degus, but not in the gerbil. In Exp II, pretreatment with captopril (50 mg/kg), an angiotensin converting enzyme inhibitor, prevented the endogenous conversion of sc injected [des-Asp–1]-AI to AIII and prevented drinking in rats and degus. The pharmacological artifact of hypovolemia caused by angiotensin-induced increases in vascular permeability was not observed in members of these species. In Exp III, blood pressure changes resulting from injections of AII and AIII in rats and gerbils were measured. Significant pressor elevations were seen following the administration of both analogs, although AII was more potent. Results demonstrate that AIII is dipsogenic in rats and degus and serves as a pressor agent in rats and gerbils. No explanation was found for the gerbil's relative lack of dipsogenicity to the presently tested angiotensins. (54 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Organ specificity of angiotensin II and Des-aspartyl angiotensin II in the conscious rat

Des-Asp angiotensin II (des-Asp AII) is a naturally occurring heptapeptide metabolite of angiotensin II (AII) which is formed by the enzymatic action of aminopeptidase A. Angiotensin II and des-Asp AII were infused into unanesthetized rats while direct mean arterial pressure, serum aldosterone and serum corticosterone were measured. Both AII and des-Asp AII caused a dose-related increase in serum aldosterone with a significant increase occurring with a dose as low as 1 ng/min. This effect was blocked by pretreatment with 1-Sar-8-Ala-angiotensin II, a competitive inhibitor of AII; however, the inhibitor was more effective in blocking the effects of AII (101%) than of des-Asp AII (82%). Both angiotensins induced a dose-related increase in serum corticosterone and mean arterial pressure. Des-Asp AII was however only 1/10 as potent as AII in elevating mean arterial pressure. 1-Sar-8-Ala-AII was also effective in inhibiting the pressor effects of AII and des-Asp AII. These data illustrate a high degree of organ specificity or selectivity for des-Asp AII and a low specificity for AII. Aminopeptidase A and leucine aminopeptidase were identified in the adrenal cortex and medulla in large amounts. Des-Asp AII may thus be formed from AII locally in the adrenal gland prior to exerting its action at that site.     

Reciprocal dopamine-glutamate modulation of release in the basal ganglia

Dopaminergic and glutamatergic transmissions have long been known to interact at multiple levels in the basal ganglia to modulate motor and cognitive functions. One important aspect of their interactions is represented by the reciprocal modulation of release. This topic has been the object of interest since the late 70's, particularly in the striatum and in midbrain dopaminergic areas (substantia nigra and ventral tegmental area). Analysis of glutamate-dopamine interactions in the control of each other's release is complicated by the fact that both glutamate and dopamine act on multiple receptor subtypes which can exert different effects. Therefore, glutamatergic modulation of dopamine release has been reviewed by analyzing the effects of glutamatergic selective receptor agonists and antagonists in the striatum (both motor and limbic portions) and in midbrain dopaminergic areas, as revealed by in vitro (slices, cell cultures, synaptosomes) and in vivo (push-pull, microdialysis and voltammetry techniques) experimental approaches. The same approach has been followed for dopaminergic modulation of glutamate release. The facilitatory nature of glutamate modulating both presynaptic and dendritic dopamine release has clearly emerged from in vitro studies. However, evidence is presented that, at least in the striatum and in the nucleus accumbens of awake rats, glutamate-mediated inhibitory effects may also occur. In vitro and in vivo experiments in the striatum and midbrain dopaminergic areas mainly depict dopamine as an inhibitory modulator of glutamate release. However, in vivo studies reporting dopamine D1 receptor mediated facilitatory effects are also considered. Therefore, the general notion that glutamate and dopamine act oppositely to regulate each other's release, is only partly supported by the available data. Conversely, the nature of the interaction between the two neurotransmitters seems to vary depending on the experimental approach, the brain area considered and the subtype of receptor involved.     

The effect of catecholaminergic depletion within the prelimbic and infralimbic medial prefrontal cortex on recognition memory for recency, location, and objects.

There is good evidence that the medial prefrontal cortex (mPFC) is involved in different aspects of recognition memory. However, the mPFC is a heterogeneous structure, and the contribution of the prelimbic (PL) and infralimbic (IL) cortices to recognition memory has not been investigated. Similarly, the role of different neuromodulators within the mPFC in these processes is poorly understood. To this end, we tested animals with 6-hydroxydopamine (6-OHDA) lesions of the PL and IL mPFC on three tests of object recognition memory that required judgments about recency, object location, and object identity. In the recency task, lesions to both PL and IL severely impaired animals' ability to differentiate between old (earlier presented) and recently presented familiar objects. Relative to sham and PL animals, the IL lesion also disrupted performance on the object location task. However, both lesions left novel object recognition intact. These data confirm previous reports that the mPFC is not required for discriminations based on the relative familiarity of individual objects. However, these results demonstrate that catecholamines within the PL cortex are crucial for relative recency judgments and suggest a possible role for neural processing within the IL in the integration of information about object location. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Context- but not familiarity-dependent forms of object recognition are impaired following excitotoxic hippocampal lesions in rats.

Dual-process models of recognition memory in animals propose that recognition memory is supported by two independent processes that reflect the operation of distinct brain structures: a familiarity process that operates independently of the hippocampus and a context-dependent (episodic) memory process that is dependent on the hippocampus. A novel variant of an object recognition procedure was used to examine this proposal. Healthy rats showed a preference for exploring a novel object rather than a familiar object: a familiarity-dependent recognition effect. They also showed a preference for exploring a familiar object that was presented in a different spatiotemporal context rather than a familiar object that was presented either in a different spatial or temporal context: a context-dependent form of recognition that is sensitive to "what" object has been presented "where" and "when." Rats with excitotoxic hippocampal lesions showed the familiarity-dependent but not the context-dependent form of recognition. The results provide support for dual-process theories of recognition memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of frontal and perirhinal cortices in visual object recognition memory in monkeys

Monkeys were trained preoperatively in visual object recognition memory. The task was delayed matching-to-sample with lists of trial-unique randomly generated visual stimuli in an automated apparatus, and the stimuli were 2D visual objects made from randomly generated coloured shapes. We then examined the effect of either: (i) disconnecting the frontal cortex in one hemisphere from the perirhinal cortex in the contralateral hemisphere by crossed unilateral ablations; (ii) disconnecting the magnocellular portion of the mediodorsal (MDmc) thalamic nucleus in one hemisphere from the perirhinal cortex in the contralateral hemisphere; or (iii) bilaterally ablating first the amygdala, then adding fornix transection, then finally perirhinal cortex ablation. We found that both frontal/perirhinal and MDmc/perirhinal disconnection had a large effect on visual object recognition memory, whereas both amygdalectomy and the addition of fornix transection had only a mild effect. We conclude that the frontal lobe needs to interact with the perirhinal cortex within the same hemisphere for visual object recognition memory, but that routes through the amygdala and hippocampus are not of primary importance.     

Dissociable roles of dopamine within the core and medial shell of the nucleus accumbens in memory for objects and place.

There is increasing focus on the role of the nucleus accumbens (NAc) in learning and memory, but there is little consensus as to how the core and medial shell subregions of the NAc contribute to these processes. In the current experiments, we used spontaneous object recognition to test rats with 6-hydroxydopamine lesions targeted at the core or medial shell of the NAc on a familiarity discrimination task and a location discrimination task. In the object recognition variant, control animals were able to discriminate the novel object at both 24-hr and 5-min delay. However, in the lesion groups, performance was systematically related to dopamine (DA) levels in the core but not the shell. In the location recognition task, sham-operated animals readily detected the object displacement at test. In the lesion groups, performance impairment was systematically related to DA levels in the shell but not the core. These results suggest that dopamine function within distinct subregions of the NAc plays dissociable roles in the modulation of memory for objects and place. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Similarities and differences in spatial learning and object recognition between young male C57Bl/6J mice and Sprague-Dawley rats.

Mice and rats are often used interchangeably in neuroscience research. However, species differences in brain structure and connectivity exist within the medial temporal lobe circuits that contribute to learning and memory. The hippocampus in particular contributes to both spatial learning and recognition memory, but the extent to which rats and mice are comparable in these two cognitive domains remains unclear. To evaluate potential species differences in spatial memory and object recognition, young adult male Sprague–Dawley rats and male C57Bl/6J mice were tested in the water maze and novel object recognition tasks. Following six days of training, with four trials per day, there was no difference in the ability of rats and mice to learn the location of a hidden platform. However, rats performed better than mice on the probe trial, indicative of superior retention. In the novel object preference test, no species differences in recognition memory were detected, although rats spent more time exploring the arena and took longer to approach the objects. These observations suggest that while species differences in spatial memory retention are present, they do not correlate with differences in object recognition memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)