PubMed Health⌕ Search

Biomedical subjects

R F Ackermann

Publications and source records attributed to R F Ackermann.

At least 55 records · Page 3Linked to original sources

Intracranial self-stimulation: temporal interactions among mesencephalic and diencephalic sites.

The monophasic pulse pair technique has been employed to ascertain whether pairs of intracranial self-stimulation (ICSS) sites interact with each other. The present study investigated the interactive properties of ICSS placements in the substantia nigra (SN) and mid-ventral periaqueductal gray (MV) with those hypothalamic ICSS placements within (MFB) or outside of (non MFB) the medial forebrain bundle. ICSS response rates when pulses of each pulse pair were split between two ICSS sites were significantly higher than the sum of rates when each site was stimulated singly with single-pulse trains. Moreover, all interaction conditions yielded higher rates than pulse pairs delivered to the mesencephalic site at an optimal interval, yet similar rates to pulse pair stimulation delivered to the diencephalic site. The symmetry of the interactions depended upon electrode loci: MV/MFB and SN/non MFB interactions were significantly higher when the mesencephalic site received the first pulse of each pair, effects which accounted for 49 and 58% of the variance respectively. Conversely, MV/non MFB and SN/MFB interactions were significantly higher when the mesencephalic site received the second pulse of each pair, effects which accounted for 5 and 14% of the variance respectively. These behavioral ICSS interactions are discussed in terms of interrelated heterogeneous subsystems subserving ICSS behavior.

Animals↗

Evaluation of [123I]isopropyliodoamphetamine as a tracer for local cerebral blood flow using direct autoradiographic comparison.

We investigated [123I]isopropyliodoamphetamine (IMP) for potential use in the autoradiographic determination of local cerebral blood flow (LCBF) in animals. The technique of direct autoradiographic comparison, derived from double radionuclide autoradiography, was used to compare the simultaneous uptakes of IMP and [14C]iodoantipyrine (IAP), a reference tracer, in awake and anesthetized rats. This new technique offers several advantages over the previously developed methods of comparing tracers, brain uptake index and first pass extraction ratio. These include the avoidance of disrupting normal cerebral blood-brain tracer exchange and the ability to compare uptakes at substructural levels, whereas the other methods are limited to larger areas. Mean values of LCBF obtained with IMP agreed closely with those using IAP, from 20 to 300 ml/100 g/min. Because IMP was found to have an extremely high effective brain:blood partition coefficient, approximately 25:1, a linear uptake tracer model could be used for IMP yielding more precise values than could IAP for LCBF values above 150. IMP was found to measure choroid plexus flows much more accurately than IAP, values being greater than 500 for IMP compared to approximately 200 for IAP. Because the mechanism of the extremely high partition coefficient of IMP is not yet defined, however, care must be used in measuring LCBF with IMP where the trapping mechanisms of normal vessels may be disrupted.

Amphetamines↗

Quantifying local cerebral blood flow by N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography.

A model was validated wherein local cerebral blood flow (LCBF) in humans was quantified by single-photon emission computed tomography (SPECT) with intravenously injected N-isopropyl-p-[123I]iodoamphetamine (IMP) combined with a modification of the classic method of arterial input sampling. After intravenous injection of IMP in rat, autoradiograms of the brain showed activity distributions in the pattern of LCBF. IMP was nearly completely removed on first pass through monkey brain after intracarotid injection (CBF=33 ml/100 g/min) and washed out with a half-time of approximately 1 hr. When the modified method of arterial input and tissue-sample counting applied to dog brain, there was good correspondence between LCBF based on IMP and on that by microsphere injection over a wide flow range. In applying the method to human subjects using SPECT, whole-brain CBF measured 47.2 +/- 5.4 ml/100 g/min (mean +/- s.d., N=5), stable gray-white distinction persisted for over 1 hr, and the half-time for brain washout was approximately 1 hr. Perfusion deficits in patients were clearly demonstrated and quantified, comparing well with results now available from positron ECT.

Adolescent↗

Ketamine-induced rotation: interaction with GABA-transaminase inhibitors and picrotoxin.

Ketamine in a dose of 100 mg/kg (IP) produced stereotypic behavior and vigorous rotation in adult male Sprague-Dawley rats. The first rotation phase, accompanied by head swinging, was short and terminated by the anesthetic phase which lasted 20-30 min. The second rotation phase began 1-3 min after the end of the anesthetic phase. A single dose of GABA-T inhibitors, gamma-vinyl GABA (1200 mg/kg, IP) or gamma-acetylenic GABA (100 mg/kg, IP) administered 4 hours prior to ketamine, shortened the first rotation phase, increased the anesthetic phase, changed the pattern of postanesthetic rotation and reduced total and net rotation scores. Picrotoxin (3 mg/kg) given 10 min prior to ketamine tended to act in the opposite direction although none of its effects reached statistical significance.

4-Aminobutyrate Transaminase↗

Effects of gamma-acetylenic GABA and gamma-vinyl GABA on metrazol-activated, and kindled seizures.

Pretreatment of adult male Sprague-Dawley rats with a single dose of gamma-vinyl GABA (GVG) (1200 mg/kg, IP) or gamma-acetylenic GABA (GAG) (100 mg/kg, IP) did not affect the threshold of metrazol-activated generalized seizures, but increased their duration to the point of status epilepticus. In rats with epilepsy kindled by amygdaloid stimulation, a single dose of GVG (800 mg/kg, IP) and five subsequent daily administrations of GAG (80 mg/kg, IP) tended to reduce the motor manifestations of seizures leaving unaffected their electrographic pattern. The effects of GVG and GAG are attributed in part to decreased arousal. Practical implications of these findings are discussed.

Alkynes↗

Morphine and intracranial self-stimulation in the hypothalamus and dorsal brainstem: differential effects of dose, time and site.

The purpose of this study was to examine if morphine, a drug of abuse, exerts site-specific effects on intracranial self-stimulation (ICSS). Rats, implanted with dorsal brainstem (DB) and hypothalamic (HYP) electrodes, bar-pressed for ICSS at two current intensities eight hours a day during six days each of predrug saline, morphine (2.5, 5.0, 7.5 or 10.0 mg/kg) and postdrug saline conditions. There were three patterns of drug effects: "pure" depressions, "pure" facilitations and a biphasic pattern (depressions followed by facilitations). Repeated morphine administration modified the temporal patterning of these effects: shortened duration of depressions and produced earlier onsets of facilitations. Within an animal, DB electrodes displayed more depressions than the HYP electrodes. Tolerance to the depressant effects, observed frequently, occurred occasionally to the facilitative effects of morphine. The drug effects on ICSS were dissociated from those observed on other behavioral measures, and thus are not artifacts of concomitant changes in activity levels.

Animals↗

Characterization of self-stimulation elicited from rat dorsolateral pariaqueductal gray.

Rats were stereotaxically implanted with chronic bipolar electrodes aimed at the periaqueductal central gray (PCG) and were subsequently tested for intracranial self-stimulation (ICSS) behavior. Consistent and reliable ICSS behavior was elicited from both the midventral and dorsolateral portions of the PCG, the latter result occurring in loci previously reported as predominantly aversive. Midventral PCG ICSS rates were significantly higher than dorsolateral PCG ICSS rates. The higher rates were not accounted for by either current intensity used or motor artifacts. Moreover, both sites displayed reliable ICSS behavior characterized by regular low-variability rates and no seizure activity, seen with other brainstem ICSS sites, but unlike diencephalic and telencephalic ICSS behavior which is characterized by irregular bursts of responding which are highly variable and sometimes accompanied by seizures. The differential ICSS responsivity between PCG structures suggests that they may be mediated by different anatomically-localizable substrates.

Animals↗

Alteration of escape from rewarding electrical brain stimulation by D-amphetamine.

Rats were trained both to barpress for and escape from locus coeruleus, midbrain periaqueductal gray and hypothalamic stimulation. Rate-intensity functions for intracranial self-stimulation (ICSS) behavior and latency-intensity functions for escape behavior were obtained for each electrode site in each animal. Following baseline, d-amphetamine was administered and responding was compared with the saline condition for both rate-intensity and latency-intensity functions. ICSS response rates were enhanced by d-amphetamine at all loci, particularly at threshold intensities, while escape responding was biphasically affected by d-amphetamine at all loci. D-amphetamine increased escape latencies at intensities which, under saline, elicited short escape latencies, while decreasing escape latencies at intensities which, under saline, elicited long escape latencies. A significant correspondence was noted between intensities which, under the influence of d-amphetamine, both elicited longer escape latencies and higher ICSS response rates, suggesting that in both ICSS and escape paradigms, animals were titrating the duration of the stimulus train. No site-specific effects of d-amphetamine upon escape behavior were noted.

Animals↗

Comparison of behaviors elicited by electrical brain stimulation in dorsal brain stem and hypothalamus of rats.

Four brain-stimulation phenomena elicited from both dorsal brain stem and hypothalamic sites were investigated with the following results: (a) intracranial self-stimulation rate-intensity functions for dorsal brain stem and hypothalamic sites yielded very high (over 1,000 responses/15 min.) to moderate (201-500 responses/15 min.) response rates; (b) d-amphetamine produced higher response rates than either l-amphetamine or saline at both dorsal brain stem and hypothalamic sites, indicating that noradrenergic dorsal brain stem fibers (or cell bodies) support intracranial self-stimulation; (c) dorsal brain stem and hypothalamic self-stimulation sites reliably produced escape behavior; (d) simultaneous stimulation of dorsal brain stem and hypothalamic sites at subthreshold intensities interacted to produce suprathreshold response rates.

Adrenergic alpha-Agonists↗

Elevations in nociceptive thresholds following locus coeruleus lesions.

Serotonin depletion or lesions of the midbrain dorsal raphe nuclei attenuate both morphine-produced and stimulation-produced analgesia. In contrast, norepinephrine depletion enhances both types of analgesia. To extend these findings, the effects of destruction of the noradrenergic locus coeruleus (LC) upon nociceptive flinch-jump thresholds were investigated. after four preoperative baseline sessions, lesions were placed in the LC bilaterally and nociceptive thresholds were determined for up to five weeks postoperatively. The lesions were localized by monoamine histofluorescence procedures together with conventional histological staining techniques. In 9 of 13 animals, the LC or its ascending dorsal noradrenergic bundle sustained either bilateral or unilateral damage, evidenced by green fluorescent back-up caudal to the lesions. Eight of these animals demonstrated significantly increased jump thresholds. In the remaining four animals, both lesions spared the LC and nociceptive thresholds were either unchanged or significantly decreased. In three of the four, raphe damage was noted, evidenced by yellow fluorescent back-up. The results suggest apparently contrasting roles of norepinephrine and serotonin in nociception.

Adrenergic Fibers↗

Intracranial self-stimulation site specificity: the myth of current spread.

Locus-specificity of intracranial self-stimulation (ICSS) was determined for 78 electrode placements using monophasic stimulation. ICSS rate comparisons between each pole of a bipolar electrode when each served as cathode were made when the anodal source was either the other pole of the bipolar electrode or a skull screw. In hypothalamic areas, medial forebrain bundle electrode tips elicited significantly higher rates than electrode tips of the same bipolar electrodes located in perifornical or far-lateral diencephalic placements. In turn, perifornical electrode tips elicited higher rates than more dorsally or medially placed tips. In dorsal pontine areas, locus coeruleus electrode tips elicited significantly higher rates than more medially or laterally placed tips. In periaqueductal midbrain and substantia nigra placements, tips located along the midline or in the substantia nigra elicited significantly higher rates than tips located lateral to or ventral to those respective structures. Anodal locus did not change these results. These results suggest that ICSS behavior is delimited by and corresponds to neuroanatomically discrete entities and that cathodal, rather than anodal factors seem to most crucially determine ICSS integrity.

Animals↗

Effects of chronic naloxone pretreatment on amygdaloid kindling in rats.

Effects of chronic naloxone pretreatment (75 or 270 micrograms/h for 14 days) on the development of amygdaloid kindling in rats were evaluated. The acquisition of seizure activity was modified in the naloxone pretreated animals, depending on the nucleus stimulated: facilitation of stages IV and V occurred in 37%, variability of electrographic and behavioral responses to electrical stimulation during the kindling development in 33%, and facilitation of stages IV and V followed by long periods of seizure suppression in 29%. Enhancement of postictal seizure suppression during a recycling paradigm was observed in all the naloxone pretreated rats. It was concluded that the chronic administration of naloxone (known to induce opioid binding upregulation and supersensitivity), in association with the enduring changes in opioid mechanisms provoked by kindled seizures, were responsible for the facilitation and suppression of epileptic activity. These findings support bidirectional modulatory effects of opioid peptides on epileptic seizures as well as the view that epileptic seizures can induce enduring alterations in opioid mechanisms.

Amygdala↗