High versus low fat/sugar food affects the behavioral, but not the cortisol response of marmoset monkeys in a conditioned-place-preference task.

The effect of a high (chocolate) versus low fat/sugar (chow) food on a conditioned-place-preference (CPP) task was evaluated in marmoset monkeys. Anxiety-related behaviors and cortisol levels before and after the CPP task were also measured. Subjects were habituated to a two-compartment CPP box and then, on alternate days, had access to only one compartment during daily 15-min conditionings, for a total of 14 trials. Marmosets were provisioned with chocolate chips in the CC-paired compartment on odd-numbered trials and standard chow in the CW-paired compartment on even-numbered trials. They were then tested for preferring the CC-paired context after a 24-h interval. During the conditioning, a significantly greater amount (in kcal/trial) of chocolate was consumed than chow, yet the foraging pattern of both food types was similar. On the test trial, the time spent in the CC-paired context increased significantly compared to pre-CPP levels, yet this response was not readily predicted by baseline behavioral or cortisol levels. Also, the chocolate CPP response was positively correlated with foraging time, rather than the amount of calories consumed. The sudden absence of the food increased exploration, while the chocolate CPP effect was associated with vigilance - both anxiety-related behaviors in marmosets. This behavioral profile occurred regardless of any concomitant change or correlation with cortisol. Therefore, the high fat/sugar food was more prone to be overly consumed by the marmosets, to induce a CPP response and to lead to anxiety-related behavior in its absence.

Consumption of a highly palatable food induces a lasting place-conditioning memory in marmoset monkeys.

Highly palatible foods may induce addiction-related behaviors. However, this has yet to be established in non-human primates. Therefore, we evaluated whether marmoset monkeys (Calllithrix penicillata) acquire a conditioned-place-preference (CPP) for chocolate and if this response is detectable after a 24-h and 15-day period. Subjects were first habituated to a two-compartment CPP box and then randomly assigned to a chocolate or control group. Thereafter, they were given access to only one compartment during daily 15-min conditionings, held on six consecutive days. On each trial, the chocolate group received pieces of chocolate (50g) in this context, whereas controls were not given a food reward. Marmosets were subsequently tested for preferring this (food) paired context after a 24-h and 15-day interval. During conditioning, individual foraging and the amount of chocolate ingested by each pair of the chocolate group remained constant. However, compared to pre-CPP levels, the time spent inside/in contact with the conditioned compartment increased significantly, while the latency to first entry decreased on both post-CPP intervals. For controls, the parameters remained unaltered. Thus, chocolate induced a persistent CPP response-an aspect usually associated with drug-related rewards.

Effects of d-amphetamine on short- and long-term memory in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats.

Diverse studies indicate that the attention deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Here SHR-saline group showed significantly poor STM and LTM relative to SD and WKY saline rats. SD and WKY rats treated with d-amphetamine displayed better STM and LTM, compared to SD-vehicle, WKY-vehicle or SHR-d-amphetamine groups.

Detection and molecular characterisation of thyroid cancer precursor lesions in a specific subset of Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) represents the most common cause of hypothyroidism and nonendemic goiter, but its clinical and pathological heterogeneity opens the question if this disease should be more properly considered as a spectrum of different thyroid conditions rather than as a single nosological entity. In this study, we analysed 133 cases of HT for the expression of galectin-3, a lectin molecule involved in malignant transformation, apoptosis and cell cycle control. An unexpected expression of galectin-3 was demonstrated in a subset of HT together with the presence of HBME-1, c-met and cyclin-D1 that are also involved in malignant transformation and deregulated cell growth. Furthermore, a loss of allelic heterozygosity in a specific cancer-related chromosomal region was demonstrated in some HT harbouring galectin-3-positive follicular cells, by using laser capture microdissection. On the basis of the morphological and molecular findings we identified four subsets of HT: (a) HT with classic features of chronic autoimmune thyroiditis; (b) HT associated to hyperplastic/adenomatous lesions; (c) HT harbouring thyroid cancer precursors; (d) HT associated to unequivocal thyroid microcarcinomas. Our findings provide a well-substantiated morphological and molecular demonstration that HT may include a spectrum of different thyroid conditions ranging from chronic autoimmune thyroiditis to thyroiditis triggered by specific immune-response to cancer-related antigens.

CD44s adhesive function spontaneous and PMA-inducible CD44 cleavage are regulated at post-translational level in cells of melanocytic lineage.

Adhesion between the CD44s receptor and hyaluronic acid plays an important role in cell migration, tumour growth and progression. Although the alternative splicing of CD44 variant exons represents the principal regulatory mechanism of CD44-mediated functions, CD44v spliced variants are scantily expressed in melanoma cells. For this reason, we have investigated the possibility that post-translational modifications of the CD44 standard receptor could play a pivotal role in regulating CD44-mediated functions in melanoma. Using metabolic inhibitors of N- and O-glycosylation, as well as melanoma transfectants expressing CD44s O-glycosylation site-specific mutants, we performed structural and functional analysis of N- and O-deglycosylated CD44s molecules expressed in melanoma cells. We discovered that complete N- and O-glycosylation is not required by CD44s to be correctly expressed on the melanoma cell surface. Indeed, variably glycosylated and functionally different CD44s molecules were constitutively expressed in primary and metastatic lesions. Furthermore, we observed that changes in N- and O-glycosylation of CD44s could modulate its cleavage. In fact, spontaneous CD44s shedding was dependent on the presence of partial or complete O-glycosylation of four serine-glycine motifs localized in the membrane-proximal CD44 ectodomain. Mutation of these serine residues, as well as an extensive metabolic O-deglycosylation, strongly impaired spontaneous CD44 shedding. Furthermore, an O-glycosylation-independent mechanism of CD44 cleavage has been identified. This alternative mechanism of receptor cleavage is phorbol 12-myristate-13-acetate (PMA) inducible, mediated by metalloproteinase and requires the presence of N-linked sugar residues. Our findings demonstrate that the post-translational modification of CD44s represents the principal regulatory mechanism of CD44s-mediated functions in melanoma.

Comparative effects of lesions to the ponto-cerebellar and olivo-cerebellar pathways on motor and spatial learning in the rat.

Emerging evidence supports the role of the cerebellum in motor learning and previous studies have also shown that olivary projections to the cerebellum are involved in motor learning. Since the pontine nuclei make up the other main relay centre in the cerebro-cerebellar pathway, the purpose of the present study was to verify the involvement of the ponto-cerebellar pathway in motor and spatial learning, by comparing these functions in intact animals and in rats with selective injury of the olivary or pontine neurons. Two groups of rats were used: the first was treated with 3-acetylpyridine to destroy the inferior olivary complex, the second received electrolytic lesions of the middle cerebellar peduncle to interrupt the ponto-cerebellar pathway. Control and lesioned rats were then submitted to three tasks: unrotated rod, rota-rod at 20 r.p.m., and Morris water maze. In the first task both 3-acetylpyridine-treated rats and rats with lesions of the middle cerebellar peduncle showed static equilibrium deficiencies. Through training, however, they reached the maximal score attained by the controls. The rats submitted to the rota-rod at 20 r.p.m. obtained scores significantly inferior to the controls. The Morris water maze results indicated that the lesion of inferior olivary complex and middle cerebellar peduncle both alter learning of the spatial task. These findings show that both the ponto- and olivo-cerebellar pathways are involved in learning complex motor sequences and spatial tasks. Since both projections converge onto Purkinje cells, our results suggest an integration of these two pathways in the cerebellar control of learning mechanism.

Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions.

BACKGROUND: Thyroid cancer is the most common endocrine malignant disease, but preoperative diagnosis remains a challenge. Fine-needle aspiration cytology has greatly improved the clinical management of thyroid nodules, but the preoperative characterisation of follicular lesions is very difficult. Many patients are thus referred to surgery more for diagnosis than for therapeutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential markers of malignant thyrocytes. METHODS: Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesions (tissue specimens and cytological cell-blocks) and 226 fresh cytological samples obtained preoperatively by ultrasound-guided fine-needle aspiration of thyroid nodules (prospective analysis). The test used monoclonal antibodies specific for CD44v6 and galectin-3, the indirect avidin-biotin complex immunoperoxidase method, and 3-amino-9-ethyl-carbazole as substrate. FINDINGS: The sensitivity, specificity, positive predictive value, and diagnostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The sensitivity and specificity of galectin-3 immunodetection alone in discriminating benign from malignant thyroid lesions were more than 99% and 98% respectively, and the positive predictive value and diagnostic accuracy were 92% and 99%. INTERPRETATION: The integration of galectin-3 immunostaining with conventional cytomorphological and clinical diagnostic procedures represents a sensitive and reliable diagnostic approach for preoperative identification of thyroid carcinomas. This test method improves the diagnostic accuracy of conventional cytology and provides the molecular basis for a new nosological assignation of the not yet classified thyroid neoplasms of indeterminate malignant behaviour.

Task-dependent role for dorsal striatum metabotropic glutamate receptors in memory.

The effect of post-training intradorsal striatal infusion of metabotropic glutamate receptor (mGluR) drugs on memory consolidation processes in an inhibitory avoidance (IA) task and visible/hidden platform water maze tasks was examined. In the IA task, adult male Long-Evans rats received post-training intracaudate infusions of the broad spectrum mGluR antagonist alpha-methyl-4-carboxyphenylglycine (MCPG; 1.0, 2.0 mM/0.5 microL), the group I/II mGluR agonist 1-aminocyclopentane-1,3-carboxylic acid (ACPD; 0.5 or 1.0 microM/0.5 microL), or saline immediately following footshock training, and retention was tested 24 h later. In the visible- and hidden-platform water maze tasks, rats received post-training intracaudate infusions of ACPD (1.0 microM), MCPG (2.0 mM), or saline immediately following an eight-trial training session, followed by a retention test 24 h later. In the IA task, post-training infusion of ACPD (0.5 and 1.0 microM) or MCPG (1.0 and 2.0 mM) impaired retention. In the IA and visible-platform water maze tasks, post-training infusion of ACPD (1.0 microM), or MCPG (2.0 mM) impaired retention. In contrast, neither drug affected retention when administered post-training in the hidden-platform task, consistent with the hypothesized role of the dorsal striatum in stimulus-response habit formation. When intradorsal striatal injections were delayed 2 h post-training in the visible-platform water maze task, neither drug affected retention, indicating a time-dependent effect of the immediate post-training injections on memory consolidation. It is hypothesized that MCPG impaired memory via a blockade of postsynaptic dorsal striatal mGluR's, while the impairing effect of ACPD may have been caused by an influence of this agonist on presynaptic "autoreceptor" striatal mGluR populations.

Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules.

PURPOSE: Thyroid cancer is the most frequently occurring endocrine malignancy; however, preoperative diagnosis of some lesions, in particular those with follicular histology, is difficult, and a consistent number of not otherwise-specified "follicular nodules" are surgically resected more for diagnosis than therapeutic purposes. In this study, we investigated whether the lectin-related molecules CD44v6 and galectin-3, the expression of which is altered during deregulated cell growth and malignant transformation, could be potential markers for improving the diagnostic accuracy of conventional cytology. MATERIALS AND METHODS: A comparative immuno-chemical and molecular analysis was performed on 157 thyroid specimens representative of normal, benign, and malignant tissues, and on 36 cytologic samples obtained preoperatively by fine-needle aspiration biopsy from nonselected patients with palpable thyroid nodules. RESULTS: Normal thyrocytes did not express galectin-3 nor CD44v6. Although the expression of CD44v6 isnegligible in thyroiditis, these molecules are variably detected in benign and malignant proliferative lesions. Interestingly, galectin-3 is never expressed in benign lesions, but it is invariably detected in cancers. A comparative evaluation of CD44v6 and galectin-3 expression in thyroid malignancies demonstrated that these molecules are coexpressed at the messenger RNA and protein level in almost all lesions. CONCLUSION: Our findings suggest that CD44v6 and galectin-3 could be potential markers to preoperatively identify malignant transformed thyrocytes. Immunodetection of these molecules on cytologic specimens obtained by fine-needle aspiration biopsy is an accurate and improved method for selecting, on a molecular basis, those nodular lesions of the thyroid gland that need to be surgically resected.

Serotonergic input to cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis in the rat.

The aim of the present study was to determine, at the light microscopic level, whether the serotonergic fibers originating from the dorsal raphe nucleus (B7), median raphe nucleus (B8) and ventral tegmentum (B9) make putative synaptic contacts with cholinergic neurons of the nucleus basalis magnocellularis and substantia innominata. For this purpose, we utilized: (i) the anterograde transport of Phaseolus vulgaris leucoagglutinin combined with choline acetyltransferase immunohistochemistry; (ii) choline acetyltransferase/tryptophan hydroxylase double immunohistochemistry; and (iii) the FluoroGold retrograde tracer technique combined with tryptophan hydroxylase immunohistochemistry. Following iontophoretic injections of Phaseolus vulgaris leucoagglutinin in the dorsal raphe nucleus, labeling was observed primarily in the ventral aspects of the nucleus basalis magnocellularis and in the intermediate region of the substantia innominata. When Phaseolus vulgaris leucoagglutinin was combined with choline acetyltransferase immunohistochemistry, a close association between the Phaseolus vulgaris leucoagglutinin-positive fibers and cholinergic neurons was observed, even though the majority of the Phaseolus vulgaris leucoagglutinin-immunoreactive terminals seemed to establish contact with non-cholinergic elements. Following Phaseolus vulgaris leucoagglutinin injection in the median raphe nucleus, very few labeled fibers with no evident close contact with nucleus basalis magnocellularis and substantia innominata cholinergic neurons were observed. After tryptophan hydroxylase/choline acetyltransferase double immunohistochemistry, a plexus of serotonergic (tryptophan hydroxylase-positive) fibers in the vicinity of choline acetyltransferase-immunoreactive neurons of the substantia innominata and nucleus basalis magnocellularis was observed, and some serotonergic terminals have been shown to come into very close contact with the cholinergic cells. Most of the tryptophan hydroxylase-immunoreactive terminals seem to establish contacts with non-cholinergic cells. Following FluoroGold injection in the nucleus basalis magnocellularis and substantia innominata, the majority of retrogradely labeled neurons was observed mainly in the ventromedial cell group of the dorsal raphe nucleus. In this area, a minority of the FluoroGold-positive neurons was tryptophan hydroxylase immunoreactive. These findings show that serotonergic terminals, identified in very close association with the cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis, derive primarily from the B7 serotonergic cell group of the dorsal raphe nucleus, and provide the neuroanatomical evidence for a direct functional interaction between these two neurotransmitter systems in the basal forebrain.

Strain-dependent involvement of D1 and D2 dopamine receptors in muscarinic cholinergic influences on memory storage.

These experiments examined the interaction of muscarinic and dopaminergic systems in influencing memory for one-trial inhibitory avoidance training in mice of the C57BL/6 and DBA/2 strains. In both strains, immediate post-training systemic administration of the muscarinic cholinergic agonist oxotremorine enhanced retention and the cholinergic antagonist atropine impaired retention. No effects were seen with injections 2 h post-training. Furthermore, the drugs did not affect retention performance of animals that received no footshock on the training trial. These results confirm previous findings indicating that muscarinic cholinergic drugs affect memory by influencing memory consolidation. In C57 mice, pretreatment with selective D1 or D2 dopamine (DA) receptor agonists (SKF 38393 or LY 171555, respectively) in otherwise non-effective doses (5 and 0.25 mg/kg, respectively) potentiated the effects of oxotremorine (0.04 mg/kg). Furthermore, in C57 mice pretreatment with selective D1 or D2 receptor antagonists (SCH 23390 or (-)-sulpiride) in otherwise non-effective doses (0.025 and 6 mg/kg, respectively) blocked the memory enhancing effects of oxotremorine. The memory impairing effects of atropine (3 mg/kg) were blocked by the D1 and D2 selective agonists and potentiated by the selective D1 or D2 antagonists. In contrast, in DBA mice, the D1 and D2 selective agonists antagonised the memory enhancing effects of oxotremorine (0.02 mg/kg) and potentiated the effects of atropine (2 mg/kg). Furthermore, the D1 and D2 antagonists potentiated the effects of oxotremorine and antagonised those of atropine. These findings indicate that although muscarinic cholinergic influences on memory storage are comparable in mice of these two strains, the cholinergic-dopaminergic interactions are opposite in the two strains. These results have implications for hypotheses of cholinergic and dopaminergic regulation of memory storage.

Angiomyofibroblastoma and aggressive angiomyxoma: two benign mesenchymal neoplasms of the female genital tract. An immunohistochemical study.

We describe a rare case of angiomyofibroblastoma (AMF) of the vulva and one case of aggressive angiomyxoma (AAM) of the pelvic region and, with the help of an extensive revision of the literature, we attempt to define their histogenesis and peculiar biological behaviour by an immunohistological evaluation. Our results indicate that AAM, which is characterized by the presence of a high content of glycosaminoglycans in the stroma, expresses uniformly vimentin and hyaluronate receptor CD44, and heterogeneously muscle specific actin (MSA) and desmin, while AMF displays a positive reaction for vimentin, desmin and laminin, and only a weak and heterogeneous positivity for CD44. Both AMF and AAM showed no immunohistochemical reactivity for alpha-smooth muscle actin (ASMA), myoglobin, cytokeratin, collagen type IV, CD68 and S-100. The stromal cells of AAM were negative for laminin. These findings support the suggestion of an origin of the two entities by a common myofibroblastic progenitor, which normally occurs in the lower female genital tract and subsequently undergoes a neoplastic transformation. The expression of CD44 by AAM, which has never been reported before, could be responsible for its more aggressive behaviour, because this receptor is able to mediate migration of neoplastic cells on a hyaluronate rich extracellular matrix. It is speculated that the neoplastic cell of the AAM and AMF of the vulva is a specific myofibroblast which probably arises from undifferentiated mesenchymal cells normally occurring in the lower female genital tract.

Structural variability of CD44v molecules and reliability of immunodetection of CD44 isoforms using mAbs specific for CD44 variant exon products.

CD44 can be considered structurally and functionally one of the most variable surface molecules. Alternative splicing of variant exons as well as posttranslational modifications of the molecule (differences in glycosylation) generate a rich repertoire of CD44 isoforms (CD44v), some of which seem to play a key role in tumor growth and progression. Immunodetection of CD44 isoforms in vivo, using mAbs specific for CD44 variant exon products, is largely used to identify those CD44 molecules involved in tumor growth and progression and to interfere with CD44-mediated processes. In the present work we demonstrate that the immunoreactivity of some mAbs directed to CD44 exon-specific epitopes can be impaired by the structural variability of the molecule. Our findings demonstrate that (1) specific exon assortment and/or posttranslational modifications of CD44v molecules can mask CD44 exon-specific epitopes; (2) glycosaminoglycan side chains, carried by some CD44v isoforms of high molecular weight, may play a critical role in determining the exact conformation of the molecule, which is necessary for the detection of CD44 variant epitopes by specific mAbs; and (3) in a panel of stable transfectants expressing CD44 N-glycosylation site-specific mutants, generated in the constant region of CD44 extracellular domain, asparagine-isoleucine substitution is sufficient per se to impair the immunoreactivity of several mAbs to pan-CD44. Thus, conformational changes due to the alternative splicing of CD44 variant exons and/or posttranslational modifications of the molecule (different degree of glycosylation), which are cell type-specific, are likely to generate CD44 variants that elude immunodetection. These findings strongly suggest that immunohistochemical analysis of CD44 expression in vitro and in vivo, using mAbs specific for CD44 variant exon epitopes, can potentially be impaired by a large number of false negative results.

The effect of intrastriatal injection of liposome-entrapped tyrosinase on the dopamine levels in the rat brain.

Parkinson's disease is a neurodegenerative disorder which is mainly characterized by degeneration of the dopaminergic cells in the nigro-striatal system. Due to a lowered L-tyrosine 3-monooxygenase activity, L-tyrosine is not sufficiently transformed to L-DOPA. To date the most common therapy is the administration of the dopamine precursor L-DOPA, with severe collateral effects. Therefore, the substitution of the lacking tyrosine hydroxylase with tyrosinase might be a novel therapeutical approach that would generate specifically L-DOPA from L-tyrosine. We present here evidence that stereotaxic injection of liposome-entrapped tyrosinase is able to significatively increase the levels of dopamine in the rat brain. The catecholamines L-DOPA, dopamine, L-epinephrine, L-norepinephrine were extracted by acid treatment from the brains and detected by HPLC.

Oxygen uptake, heart rate and blood lactate concentration during a normal training session of an aerobic dance class.

The aim of this research was to investigate the physiological responses and, in particular, the participation of lactic acid anaerobic metabolism in aerobic dance, which is claimed to be pure aerobic exercise. In contrast to previous studies, that have put subjects in very unfamiliar situations, the parameters were monitored in the familiar context of gymnasium, practice routine and habitual instructor. A group of 30 skilled fairly well-trained women performed their usual routine, a combination of the two styles: low (LI) and high impact (HI), and were continuously monitored for heart rate (HR) and every 8 min for blood lactate concentration ([La-]b). Of the group, 15 were tested to determine their maximal aerobic power (VO2max) using a cycle-ergometer. They were also monitored during the routine for oxygen uptake (VO2) by a light telemetric apparatus. The oxygen pulses of the routine and of the corresponding exercise intensity in the incremental test were not statistically different. The mean values in the exercise session were: peak HR 92.8 (SD 7.8)% of the subject's maximal theoretical value, peak VO2 99.5 (SD 12.4)% of VO2max, maximal [La-]b 6.1 (SD 1.7) mmol x l(-1), and mean 4.8 (SD 1.3) mmol x l(-1). Repeated measures ANOVA found statistically significant differences between the increasing [La-]b values (P < 0.001). In particular, the difference between the [La-]b values at the end of the mainly LI phase and those of the LI-HI combination phase, and the difference between the samples during the combination LI-HI phase were both statistically significant (both P = 0.002 and P = 0.002). The similar oxygen pulses confirmed the validity of the present experiment design and the reliability of HR monitoring in this activity. The HR, VO2 and, above all, the increase of [La-]b to quite high values, showing a non steady state, demonstrated the high metabolic demand made by this activity that involved lactic acid metabolism at a much higher level than expected.

Strain-dependent effects of D2 dopaminergic and muscarinic-cholinergic agonists and antagonists on memory consolidation processes in mice.

The interaction between muscarinic-cholinergic and dopaminergic systems in the modulation of memory storage of Y-maze discrimination (YMD) task was examined in C57BL/6 and DBA/2 strains of mice. In C57BL/6 mice, post-training systemic (i.p.) administration of the D2-agonist quinpirole facilitated retention and the D2-antagonist (-)-sulpiride impaired retention. Opposite effects were observed in DBA/2 strain. The facilitating or impairing effects of quinpirole and (-)-sulpiride were blocked by simultaneous post-training administration of muscarinic-cholinergic agonists and antagonists. The memory enhancing effects of the cholinergic agonist oxotremorine were not blocked by simultaneous administration of sulpiride in C57BL/6 mice or quinpirole in DBA/2 mice. Furthermore, the memory impairing effects of the cholinergic antagonist atropine were not blocked by simultaneous administration of quinpirole in C57BL/6 mice or sulpiride in DBA/2 mice. These findings indicate that the effects of D2-receptor agonists and antagonists on retention of YMD task are strain-dependent and mediated through muscarinic-cholinergic mechanisms.

The dopaminergic mesencephalic projections to the hippocampal formation in the rat.

1. The dopaminergic mesencephalic neurons projecting to the hippocampal formation are distributed in three cell groups: A8 region in the retrorubral field, A9 region in the substantia nigra and A10 region in the ventral tegmental area. 2. Anterograde and retrograde tract-tracing techniques combined with immunohistochemical procedures indicate a topographical organization of mesencephalic dopaminergic projections towards the hippocampal formation. 3. Electrophysiological evidence suggest that dopaminergic mesencephalic neurons could have a regulatory role in suppressing hippocampal excitability. 4. The functional significance of the mesohippocampal dopaminergic system is largely unknown, although it was suggested that this projection could have a role in methamphetamine-produced hypermotility and in modulation of memory processes.