Morphometric analysis of ventral mesencephalic neurons retrogradely labeled with Fluoro-Gold following injections in the shell, core and rostral pole of the rat nucleus accumbens

Morphologically distinct subsets of mesotelencephalic neurons were sought following retrograde transport of Fluoro-Gold from iontophoretic injections relatively restricted to the medial shell, core or rostral pole subterritories of the nucleus accumbens. The diameters and lengths of Fluoro-Gold immunolabeled dendrites of medial shell-projecting neurons were less than those of core and rostral pole-projecting neurons.     

Estrogen effects on the tuberoinfundibular dopaminergic system in the female rat brain

Estrogen effects on tyrosine hydroxylase (TH), monoamine oxidase types A and B (MAO), and dopamine (DA) in microdissected regions of the hypothalamus, preoptic area and substantia nigra (SNR) of the female rat brain were investigated. Ovariectomized (OVX) young adult female rats were implanted with single silastic capsules containing 100% estradiol valerate (EV). Control rats received empty silastic capsules. Two weeks following capsule insertion, EV decreased TH activity and DA concentration in the arcuate nucleus (AN) while no significant changes in TH activity or DA concentration were observed in the SNR, ventromedial nucleus (VMN), suprachiasmatic nucleus, paraventricular nucleus, medial preoptic nucleus, or the periventricular preoptic nucleus. Although estrogen suppressed TH and DA in the AN, 2 weeks following removal of the estrogen containing capsules, TH activity and DA concentration were restored to control (OVX) levels. Suppression of MAO activity occurred in both the AN and the VMN of rats implanted with EV capsules and returned to OVX levels following the removal of the estradiol load. These results revealed that estrogen effects on TH and MAO activities and DA concentration in the midbrain are region specific and reversible; and that among the dopaminergic systems studied, estrogen effects on TH and DA are confined to the tuberoinfundibular dopaminergic system (TIDAS). Furthermore, these results support our hypothesis that estrogen is a key regulator of DA function in the TIDAS via effects on TH. The importance of these findings to the control of gonadotropin secretion and reproductive cyclicity is discussed.     

Leptin and interleukin-6 alter the function of mesolimbic dopamine neurons in a rodent model of prenatal inflammation

Maternal inflammation during critical stages of gestation is thought to underlie the link between prenatal infection and several neurodevelopmental psychiatric disorders in the offspring, including schizophrenia. Increased activity of mesolimbic dopamine (DA) neurons, a hallmark of psychosis, is found in offspring of rodents exposed to a prenatal inflammatory challenge but it is unclear how this effect is elicited. Using an experimental model of localized aseptic inflammation with turpentine oil (TURP) we sought to establish whether circulating interleukin-6 (IL-6) and leptin play a role in the effects of prenatal inflammation on DA neurons. Both mediators are involved in the systemic inflammatory response to immunogens, with IL-6 mediating the early phase, followed by leptin in the late phase of the response. Maternal treatment with TURP at gestational day (GD) 15 enhanced the locomotor response to the DA indirect agonist, amphetamine (AMPH), increased the expression of tyrosine hydroxylase (TH), an enzyme involved in DA synthesis, DA levels and the expression of the post-synaptic protein spinophilin in the nucleus accumbens (NAcc) in the adult offspring. All of these alterations were totally abolished by co-treating the pregnant dams with a neutralizing IL-6 antiserum. Neutralization of maternal leptin prevented the enhanced behavioral sensitization and elevation of DA and spinophilin in the NAcc but spared other changes regulated by IL-6, such as increased NAcc TH levels and acute locomotor response to AMPH. Our results provide novel evidence to suggest that prenatal surges in both maternal circulating IL-6 and leptin contribute to the appearance of sensitized DA function in the adult offspring.     

Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.     

PET studies of somatosensory processing of light touch

This study aimed at investigating the neural substrates of spatial and non-spatial Behavioural components of exploration to novelty by a neurogenetic approach. Thus, functional imaging and Behavioural analysis were carried out in the Naples High-Excitability (NHE) rats, a model of hyperactivity and attention-deficit. Quantitative cytochrome oxidase (C.O.) histochemistry was used to measure the basal metabolic capacity of different forebrain structures. In parallel experiments, exploration in an 8-arm radial maze (Olton-maze) with extra-maze cues was used to measure attentional, motivational and spatial components of Behaviour after feeding rats’ ad-libitum or at a reduced diet. Functional imaging analysis: brains from naive rats were stained for quantitative C.O. histochemistry along with standards. NHE rats showed lower C.O. activity in perirhinal and posterior-parietal cortex (all layers) and cortical amygdala, and greater activity in entorhinal cortex (superficial layers). The outer granular cell layer of the dentate gyrus had greater activity in NHE. Behavioural analysis: at low and high motivational level, maze exploration was reinforced during shaping throughout and then only a single arm. The Behaviour was monitored by a CCD camera and videotaped. (i) There was no line difference in working memory during non reinforced maze exploration, independent of the motivational level; (ii) during shaping with all baited arms, there was no line difference in working memory, but NHE rats showed a very low or lower food consumption at low and high motivational level, respectively; (iii) rats showed a higher working memory in finding the single baited arm at high motivational level; (iv) NHE rats paid little attention towards reinforcement upon visiting the baited arm only at low motivational level. Thus, Behavioural and functional neuroimaging analysis suggests the neural substrates of spatial and non-spatial components of exploration to be underlined by different network operations in the neocortical and limbic cortices in the NHE rat lines. Therefore, they appear as an useful tool to the understanding of Attention-Deficit Hyperactivity Disorder (ADHD) in children. (Supported by Telethon–Italy grant E.513).     

Effects of rubral microinjections of muscimol and bicuculline in a genetic animal model of paroxysmal dystonia

Previous studies suggested that GABAergic dysfunctions within the red nucleus are involved in stress-inducible paroxysmal dystonia of the dt(sz) mutant hamster. In the present study, rubral microinjections of the GABAA receptor agonist muscimol exerted only moderate antidystonic effects and the antagonist bicuculline failed to show significant effects on the severity of dystonia. These data indicate that disturbed rubral GABAergic inhibition is not important for the manifestation of dystonia in the dt(sz) mutant.     

Deficient reinforcement learning in medial frontal cortex as a model of dopamine-related motivational deficits in ADHD

Attention Deficit/Hyperactivity Disorder (ADHD) is a pathophysiologically complex and heterogeneous condition with both cognitive and motivational components. We propose a novel computational hypothesis of motivational deficits in ADHD, drawing together recent evidence on the role of anterior cingulate cortex (ACC) and associated mesolimbic dopamine circuits in both reinforcement learning and ADHD. Based on findings of dopamine dysregulation and ACC involvement in ADHD we simulated a lesion in a previously validated computational model of ACC (Reward Value and Prediction Model, RVPM). We explored the effects of the lesion on the processing of reinforcement signals. We tested specific behavioral predictions about the profile of reinforcement-related deficits in ADHD in three experimental contexts; probability tracking task, partial and continuous reward schedules, and immediate versus delayed rewards. In addition, predictions were made at the neurophysiological level. Behavioral and neurophysiological predictions from the RVPM-based lesion-model of motivational dysfunction in ADHD were confirmed by data from previously published studies. RVPM represents a promising model of ADHD reinforcement learning suggesting that ACC dysregulation might play a role in the pathogenesis of motivational deficits in ADHD. However, more behavioral and neurophysiological studies are required to test core predictions of the model. In addition, the interaction with different brain networks underpinning other aspects of ADHD neuropathology (i.e., executive function) needs to be better understood.     

Bilateral effects of unilateral GDNF administration on dopamine- and GABA-regulating proteins in the rat nigrostriatal system

Dopamine (DA) affects GABA neuronal function in the striatum and together these neurotransmitters play a large role in locomotor function. We recently reported that unilateral striatal administration of GDNF, a growth factor that has neurotrophic effects on DA neurons and enhances DA release, bilaterally increased striatal neuron activity related to locomotion in aged rats. We hypothesized that the GDNF enhancement of DA function and resulting bilateral enhancement of striatal neuronal activity was due to prolonged bilateral changes in DA- and GABA-regulating proteins. Therefore in these studies we assessed dopamine- and GABA-regulating proteins in the striatum and substantia nigra (SN) of 24 month old Fischer 344 rats, 30 days after a single unilateral striatal delivery of GDNF. The nigrostriatal proteins investigated were the DA transporter (DAT), tyrosine hydroxylase (TH), and TH phosphorylation and were examined by blot-immunolabeling. The striatal GABA neuron-related proteins were examined by assay of the DA D₁ receptor, DARPP-32, DARPP-32 Thr³⁴ phosphorylation, and glutamic acid decarboxylase (GAD). Bilateral effects of GDNF on TH and DAT occurred only in the SN, as 30 μg GDNF increased ser19 phosphorylation, and 100 μg GDNF decreased DAT and TH protein levels. GDNF also produced bilateral changes in GAD protein in the striatum. A decrease in DARPP-32 occurred in the ipsilateral striatum, while increased D₁ receptor and DARPP-32 phosphorylation occurred in the contralateral striatum. The 30 μg GDNF infusion into the lateral striatum was confined to the ipsilateral striatum and substantia nigra. Thus, long-lasting bilateral effects of GDNF on proteins regulating DA and GABA neuronal function likely alter physiological properties in neurons, some with bilateral projections, associated with locomotion. Enhanced nigrostriatal excitability and DA release by GDNF may trigger these bilateral effects.     

Role of genotype in the adaptation of the brain dopamine system to stress

Behavioral and biochemical analysis of the effects of stress on brain dopamine (DA) functioning in two inbred strains of mice reveals opposite patterns of adaptation to chronic stress. Chronically stressed mice of the C57BL/6 (C57) strain are characterized by hypersensitive mesolimbic DA autoreceptors and by a dramatic increase of D1/D2 DA receptor ratio (possibly postsynaptic) in the nucleus accumbens septi (NAS) as revealed by in vivo binding of 3H-spiperone and 3H-SCH23390. Chronically stressed DBA/2 (DBA) mice present, on the contrary, hyposensitive DA autoreceptors and no changes in the D1/D2 DA receptors ratio in this brain area. The analysis of the behavioral responses of chronically stressed mice of the C57 strain to the mixed D1/D2 receptor agonist apomorphine, to the selective D2 agonist LY171555 and to the selective D1 agonist SKF 38393 suggest a close relationship between the behavioral alterations produced by chronic stress and the alterations of sensitivity of D2 pre- and postsynaptic receptors in the mesolimbic system. Furthermore, chronically stressed C57 mice present a marked decrease of spontaneous-climbing behavior which is not observed in the mice of the DBA strain and is dependent on the alteration of the biphasic evolution of this behavior during exposure to the test situation which, for these mice, represents a novel environment. Acute exposure to aversive environmental conditions induces a biphasic alteration of DA transmission (initial increase of DA release followed by a decrease under control levels) in the NAS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system.

We studied levels of neurofilament (NF) proteins in the ventral tegmental area (VTA), and other regions of the central nervous system, of two genetically inbred rat strains, Lewis (LEW) and Fischer (F344) rats. These strains represent genetically divergent populations of rats that have been used to study possible genetic factors involved in a variety of biological processes, including drug addiction: compared to F344 rats, LEW rats show a much higher preference for several classes of drugs of abuse. We found 30-50% lower levels of three NF proteins, NF-200 (NF-H), NF-160 (NF-M), and NF-68 (NF-L), in the VTA of LEW compared to F344 rats by use of immunolabeling and Coomassie blue staining. These strain differences were highly specific to this brain region, with no differences observed elsewhere in brain or spinal cord. Interestingly, chronic treatment of F344 rats with morphine decreased levels of these three NF proteins in the VTA, as found previously in outbred Sprague-Dawley rats (Beitner-Johnson, D., Guitart, X., and Nestler, E.J.:J. Neurosci., 12:2165-2176, 1992), whereas morphine had no effect on NF levels in the VTA of LEW rats. A similar strain difference was observed in chronic morphine regulation of tyrosine hydroxylase, with morphine increasing enzyme immunoreactivity in the VTA of F344 rats (as has been observed previously in Sprague-Dawley rats [Beitner-Johnson, D., and Nestler, E.J.:J. Neurochem., 57:344-347, 1991]), but not in LEW rats. In view of the observations that LEW and F344 rats show different levels of preference for several types of drugs of abuse, and of the evidence supporting a central role of the mesolimbic dopamine system in drug reward mechanisms, the results of the current study suggest the possibility that levels of NFs and tyrosine hydroxylase may mediate some aspects of drug reinforcement and contribute to individual genetic differences in vulnerability to drug addiction.     

Neurochemical plasticity in the enteric nervous system of a primate animal model of experimental Parkinsonism

Abstract  Emerging evidences suggest that the enteric nervous system (ENS) is affected by the degenerative process in Parkinson's disease (PD). In addition lesions in the ENS could be associated with gastrointestinal (GI) dysfunctions, in particular constipation, observed in PD. However, the precise alterations of the ENS and especially the changes in the neurochemical phenotype remain largely unknown both in PD and experimental Parkinsonism. The aim of our study was thus to characterize the neurochemical coding of the ENS in the colon of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, a well-characterized model of PD. In the myenteric plexus, there was a significant increase in the number of neurons per ganglia (identified with Hu), especially nitric oxide synthase immunoreactives (IR) neurons in MPTP-treated monkeys compared to controls. A concomitant 72% decrease in the number of tyrosine hydroxylase-IR neurons was observed in MPTP-treated monkeys compared to controls. In contrast no change in the cholinergic or vasoactive intestinal peptide-IR population was observed. In addition, the density of enteric glial cells was not modified in MPTP-treated monkeys. Our results demonstrate that MPTP induces major changes in the myenteric plexus and to a lesser extent in the submucosal plexus of monkeys. They further reinforce the observation that lesions of the ENS occur in the course of PD that might be related to the GI dysfunction observed in this pathology.     

The limits of motivational influence in ADHD: no evidence for an altered reaction to negative reinforcement

Functional magnetic resonance imaging studies have reported a diminished response in the brain’s reward circuits to contingent cues predicting future monetary gain in adolescents with attention-deficit/hyperactivity disorder (ADHD). The situation with regard to monetary loss is less clear, despite recognition that both positive and negative consequences impact ADHD behaviour. Here, we employ a new Escape Monetary Loss Incentive task in an MRI scanner, which allows the differentiation of contingency and valence effects during loss avoidance, to examine ADHD-related alterations in monetary loss processing. There was no evidence of atypical processing of contingent or non-contingent monetary loss cues in ADHD — either in terms of ratings of emotional and motivational significance or brain responses. This suggests that the ability to process contingencies between performance and negative outcomes is intact in ADHD and that individuals with ADHD are no more (or less) sensitive to negative outcomes than controls. This latter finding stands in stark contrast to recent evidence from a similar task of atypical emotion network recruitment (e.g. amygdala) in ADHD individuals to cues predicting another negative event, the imposition of delay, suggesting marked specificity in the way they respond to negative events.     

Chromogranin A applied to the nucleus accumbens decreases locomotor activity induced by activation of the mesolimbic dopaminergic system in the rat

The aim of the study was to obtain supporting evidence, using a behavioral paradigm, of the hypothesis that chromogranin A attenuates transmitter release in the CNS. We studied the effects of chromogranin A injected into the nucleus accumbens on locomotor activity triggered by application of picrotoxin into the ventral tegmental area of rats. Injection of picrotoxin into the ventral tegmental area, which is known to disinhibit dopaminergic mesolimbic neurons, caused a significant increase in horizontal activity. Distance covered during locomotion and movement time increased more than twofold, whereas stereotypy time and number, indices of nonlocomotor behavior, were not significantly affected by picrotoxin. Pressure injection of Chromogranin A into the nucleus accumbens prior to injection of picrotoxin into the ventral tegmental area prevented these locomotor effects and had little or no effect on nonlocomotor behavior. Similarly, the picrotoxin-induced activity was prevented by injecting cobalt chloride into the nucleus accumbens. The results show that chromogranin A has an attenuating effect, either directly or indirectly, on dopaminergic neurotransmission in the nucleus accumbens that can be exemplified by inhibiting picrotoxin-induced locomotor activity. Further studies are needed to determine the mechanism of chromogranin A action in the nucleus accumbens.     

Evidence for an altered architecture and a hierarchical modulation of inhibitory control processes in ADHD

Inhibitory control deficits are a hallmark in ADHD. Yet, inhibitory control includes a multitude of entities (e.g. ‘inhibition of interferences’ and ‘action inhibition’). Examining the interplay between these kinds of inhibitory control provides insights into the architecture of inhibitory control in ADHD. Combining a Simon task and a Go/Nogo task, we assessed the interplay of ‘inhibition of interferences’ and ‘action inhibition’. This was combined with EEG recordings, EEG data decomposition and source localization. Simon interference effects in Go trials were larger in ADHD. At the neurophysiological level, this insufficient inhibition of interferences in ADHD related to the superior parietal cortex. Simon interference effects were absent in action inhibition (Nogo) trials in ADHD, compared to controls. This was supported by bayesian statistics. The power of effects was higher than 95%. The differential effects between the groups were associated with modulations of neurophysiological response selection processes in the superior frontal gyrus. ADHD is not only associated with deficits in inhibitory control. Rather, the organization and architecture of the inhibitory control system is different in ADHD. Distinguishable inhibitory control processes operate on a hierarchical ‘first come, first serve’ basis and are not integrated in ADHD. This is a new facet of ADHD.     

6-Hydroxydopamine-induced lesions in a rat model of hemi-Parkinson's disease monitored by magnetic resonance imaging

Injection with 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway results in loss of nigrostriatal dopaminergic neurons, which has been used widely as an animal model of Parkinson's disease. In the present study, location and extent of lesions 1 day after 6-OHDA injections (2, 4, 8, or 16 microg as a free base) in the substantia nigra (SN) were evaluated in rats by T(2)-weighted magnetic resonance imaging (MRI). The changes in MRI were also compared to immunohistochemical and behavioral changes. Hyperintense area in MRI was found at the region corresponding to 6-OHDA injection in a dose-dependent manner and was accompanied by a loss of tyrosine hydroxylase (TH)-positive cells. The shape of hyperintense area in the SN appeared to be composed of two components (i.e., circular and longitudinal regions). Administration of a larger dose of 6-OHDA (8-16 microg) was accompanied by an increase in hyperintense area and loss of TH-positive cells beyond the SN. The hyperintense area was observed on the first and third days after 6-OHDA injection, but the size and intensity declined to near normal levels on the ninth day. Rotational behavior induced by methamphetamine reached maximal levels at 4 microg 6-OHDA, and the behavior was maintained with doses up to 16 microg of 6-OHDA. Intrastriatal injection with 6-OHDA was less effective. These results suggest that MRI provides highly valuable information for verifying the size and location of intended lesions as well as for determining the optimal dose of neurotoxins in individual animals.     

Behavioural, pharmacological, morpho-functional molecular studies reveal a hyperfunctioning mesocortical dopamine system in an animal model of attention deficit and hyperactivity disorder

Clinical and experimental evidence suggest an involvement of dopamine systems, mainly the mesocorticolimbic one (MCL), in Attention-Deficit Hyperactivity Disorder (ADHD). However, it remains to be ascertained whether the systems are hyper- or hypo-functioning, for the implications of the functional state. Indeed, differential functional states of the MCL branches are suggested to be the neural substrate of different ADHD variants. This review covers published and unpublished data from the Naples-High Excitability (NHE) rat, an animal model of ADHD, featuring its main aspects, with no hypertension. Therefore, a multiple approach based on morphological studies of dopamine, norepinephrine, glutamate, acetylcholine and GABA systems, synaptic (Calcium/Calmodulin kinase II) and extrasynaptic (chondroitin sulphates) environments, and molecular biology and pharmacological studies on the dopamine system has been carried out. Morphological findings suggest dopamine neurons in the Ventral Tegmental Area (VTA) to be hypertrophic in NHE rats. The mesostriatal and mesolimbic dopamine branches appear to be normal in basal conditions. However, the striatal interface is probably defective following activation. Conversely, the prefrontal cortex, which represents the second main target of VTA dopamine neurons, has many alterations at the basal level. Therefore, the emerging picture is the association of a hyperinnervating and hyperfunctioning mesocortical branch of the dopamine system. Thus, the evidence gathered so far might improve our understanding of the neural substrates of neuropsychiatric disorders such as ADHD, schizophrenia and drug addiction.     

A single dose model of methamphetamine-induced neurotoxicity in rats: effects on neostriatal monoamines and glial fibrillary acidic protein

The neurotoxic effects of a single administration of methamphetamine (MA) were studied under conditions conducive to MA-induced hyperthermia. After a single dose of MA (10, 20, 30, or 40 mg/kg, s.c.) or saline (3 ml/kg) to Sprague–Dawley CD rats, rectal temperatures were monitored for 9 h in a room with an ambient temperature of 22.0±0.5°C. MA induced significant dose-dependent hyperthermia, however, no significant increase in mortality occurred. Neostriatal DA, 5-HT, TH, and GFAP were assayed 3 days following treatment. MA induced dose-dependent reductions of DA, 5-HT and TH, and increased GFAP. For DA, at doses of 20, 30, or 40 mg/kg the reductions were to 71%, 49%, and 29%, and for 5-HT were to 73%, 44%, and 19% of control values. No reductions were seen after the 10 mg/kg dose. Semiquantitative analysis Western blots of TH and GFAP demonstrated that TH was reduced to 52%, 75%, and 28%, and GFAP was increased to 125%, 134%, and 149% of control values at MA doses of 20, 30, or 40 mg/kg, respectively. No significant changes in TH or GFAP were seen at the 10 mg/kg MA dose. These results demonstrate that a single-dose of MA can be as effective as the widely used four-dose every 2 h regimen. Moreover, mortality can be minimized by monitoring core body temperature and preventing MA-induced hyperthermia from exceeding 41.5°C.     

Evidence for a dopaminergic innervation of the subthalamic nucleus in the rat

The dopaminergic connection from the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) to the subthalamic nucleus in the rat was investigated using anterograde retrograde tracers. Iontophoretic injection of the retrograde tracer fluoro-gold (FG) into the subthalamic nucleus resulted in a substantial number of labeled neurons in the SNc. Immunohistochemistry of tyrosine hydroxylase (TH) confirmed the dopaminergic nature of these labeled neurons. Retrogradely labeled neurons were also found in the VTA. Injection of the anterograde tracer biocytin into the SNc produced biocytin-labeled terminals in the subthalamic nucleus hence providing clear evidence for a dopaminergic innervation of this nucleus. Quantitative analysis of labeled axons revealed that there were 15–38 terminal branches per axon, each branch being 50–150 μm long. The overall dimensions of one terminal arborization were 400 × 250 × 150 μm. There was no clear-cut topographical organization of the projection, but a slight mediolateral difference in the density of terminals. This direct dopaminergic projection is thought to interact with cortical and pallidal inputs in the subthalamic nucleus, which implies that the functions of the subthalamic nucleus are more complex than previously assumed.     

Quantitative mapping of cytovhrome oxidase activity in the central auditory system of the gerbil: a study with calibrated activity standards and metal-intensified histochemistry

The objective was to obtain detailed topographic determinations of cytochrome oxidase activity in the gerbil central auditory system at the light microscopic level. Quantitative techniques were developed using (1) tissue standards calibrated to express histochemical measures as actual enzyme activity units, (2) densitometry and image analysis of histochemical reaction product formation, (3) spectrophotometry of cytochrome oxidase activity, and (4) a cobalt-intensified staining procedure compatible with autoradiography and other techniques requiring fresh-frozen brains without perfusion-fixation. Linear relationships between incubation time, section thickness, and activity of dissected brain regions, with their reaction product measured densitometrically were determined. Auditory structures with the high activities showed about 8 times the labeling intensity of the white matter or control sections inhibited with cyanide, glutaraldehyde, or heat. This indicated the high sensitivity of the method without loss of specificity. Specific activity for each of the 18 auditory structures measured were all above the units measured for whole brain homogenates, supporting the notion that basal levels of oxidative metabolism are greater for the auditory system. There was a progressive decrement in activity from brain stem to forebrain auditory structures. The more peripheral nuclei also showed a higher proportion of somatic as compared to neuropil reactivity. In contrast, auditory midbrain and thalamocortical regions were characterized primarily by neuropil reactivity. Comparison of intrinsic patterns of activity with morphological schemes to subdivide nuclei, showed a good correspondence with classical subdivisions derived from Golgi studies. The reported activities may provide a base of normative data in the gerbil for subsequent studies of central auditory functions. The method presented fulfilled established quantitative criteria and provided a more sensitive approach for regional mapping studies of brain cytochrome oxidase activity.