Biomedical subjects

J P Huston

Publications and source records attributed to J P Huston.

At least 19 recordsLinked to original sources

PubMed2001

Evidence for a dissociation between MPTP toxicity and tyrosinase activity based on congenic mouse strain susceptibility.

The neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most valuable available models for investigating critical aspects of human Parkinson's disease. In order to analyze the relevance of pigmentation for MPTP sensitivity, we compared C57Bl/6 wild-type mice with the albino mutant C57Bl/6J-Tyr(c-2J) of the same strain. These animals were treated either with systemic MPTP or with saline and were examined in behavioral tests. Seven days after treatment, the contents of dopamine and other monoamines were determined postmortem in the neostriatum and ventral striatum. Furthermore, the numbers of tyrosine hydroxylase-positive cells were counted in the substantia nigra and ventral tegmental area. Open field testing showed that rearing activity was drastically reduced as an acute effect of MPTP in both wild type and mutants; however, subsequent recovery to control levels was faster in wild-type mice. Nest building also indicated strain-dependent effects, since it was delayed only in mutants treated with MPTP. Neurochemically, MPTP led to severe neostriatal dopamine depletions, which did not differ significantly between wild-type (72.9%) and mutant mice (82.1%). Less severe dopamine depletions were also found in the ventral striatum. Histologically, a loss of tyrosine hydroxylase-labeled cells was observed only in the substantia nigra of both wild-type and mutant mice (13.3 and 21.3%, respectively), but not in the ventral tegmental area. Together, our data do not provide evidence that tyrosinase-deficient mice are less affected by MPTP treatment than the comparable wild type, thus arguing strongly against the hypothesis that enhanced MPTP sensitivity in pigmented mouse strains is caused by tyrosinase activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2001

Dopaminergic effects of histamine administration in the nucleus accumbens and the impact of H1-receptor blockade.

The mesolimbic dopamine system is thought to play a critical role in reward-related processes. A number of studies have shown that lesion or inhibition of histaminergic neurons acting through H1 receptors can potentiate the effects of drug-induced reward (e.g., psychostimulants and opioids) and can enhance the reinforcing effects of electrical stimulation of the brain. Since dopamine transmission in the nucleus accumbens is thought to provide a crucial link in these histaminergic actions, we examined the effects of local histamine application (0.1, 1.0 and 10.0 micromol/l) on dopamine and its metabolites in the nucleus accumbens of anesthetized rats by means of unilateral reverse dialysis. To study the influence of H1 receptors, we also applied the H1-receptor antagonist pyrilamine (10.0 and 20.0 mg/kg, intraperitoneally) 20 min before histamine administration (1 mmol/l). Finally, pyrilamine (0.1, 1.0 and 10.0 micromol/l) was locally administered into the nucleus accumbens. The data show that histamine can enhance extracellular dopamine levels in the nucleus accumbens in a dose-dependent way. This increase was partially antagonized by prior peripheral administration of 10 mg/kg, and was completely blocked by 20 mg/kg, of pyrilamine. Finally, intra-accumbens administration of pyrilamine locally decreased dopamine and increased dihydroxyphenylacetic acid and homovanillic acid levels. These data are discussed with respect to the possible interactions between dopaminergic and histaminergic mechanisms in the mesolimbic system and their relation to mechanisms of reinforcement.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Behavioral effects of buspirone in the marmoset employing a predator confrontation test of fear and anxiety.

In order to further validate the recently developed marmoset (Callithrix penicillata) predator confrontation model of fear and anxiety, we investigated the behavioral effects of buspirone with this method. The apparatus consisted of three parallel arms connected at each end to a perpendicular arm, forming a figure-eight continuous maze. A taxidermized wild oncilla cat (Felis tigrina) was positioned facing a corner of the parallel arms, alternating between the left or right side of the maze among animals tested. All subjects were first submitted to seven 30-min maze habituation trials (HTs) in the absence of the predator, and then to five randomly assigned treatment trials (TTs) in the presence of the predator: three buspirone sessions (0.1, 0.5 and 1.0 mg/kg), saline and sham injection controls. Twenty minutes after treatment administration, the animal was released into the maze and had free access to the apparatus for 30 min. All trials were taped for later behavioral analysis. Buspirone significantly decreased the frequency of scent marking, while increasing the time spent in proximity to the 'predator' stimulus, indicating an anxiolytic effect. Neither locomotor activity, exposure to a novel environment, stimulus location and habituation, nor gender influenced the effects of the drug treatments. These results further validate this method and demonstrate the potential usefulness of this ethologically based paradigm to test anxiety and fear-induced avoidance in nonhuman primates and its susceptibility to anxiolytic pharmacological manipulations.

Animals↗

PubMed2001

Comparison of neurokinin SP with diazepam in effects on memory and fear parameters in the elevated T-maze free exploration paradigm.

The elevated T-maze was combined with a free exploration protocol, which, in contrast to the conventional procedure, dispenses with handling of the animals during the experimental sessions. This allows measurement of fear indexes derived from the elevated plus-maze as well as assessment of acquisition of open arm avoidance and open arm escape in one continuous session. Retention of the different fear-responses is measured 72 h later without drug treatment. In order to assess the effects of two known anxiolytics in this paradigm, rats received an IP injection of diazepam (1 to 4 mg/kg), substance P (5 to 500 microg/kg) or vehicle (1 ml/kg) and were tested on the T-maze for 5 min. Diazepam elevated open arm activity, indicative of an anxiolytic effect. The drug also increased the latency to escape from the open arms, but did not significantly affect acquisition of open arm avoidance. During the retention trial, diazepam in higher doses impaired the performance of both fear-responses, suggestive of an anterograde amnesic effect. Substance P did not influence acquisition and retention of open arm avoidance and escape. However, in high doses, the peptide increased the sojourn time in the central arena of the maze, indicating reduced fear and, hence, a dissociation between anxiolytic and amnesic effects. The present findings demonstrate that the elevated T-maze free exploration paradigm is sensitive to anxiolytic and memory-modulating effects of drugs.

Animals↗

PubMed2001

Repeated treatment with cholecystokinin octapeptide improves maze performance in aged Fischer 344 rats.

Previous studies have shown that sulfated cholecystokinin octapeptide (CCK-8S) can improve learning in adult rodents when administered systemically or into the central nucleus of amygdala. Here we analyzed the effect of repeated intraperitoneal (i.p.) injection of CCK-8S on the performance of 26-month-old Fischer 344 rats in different versions of the Morris water maze and in a rota-rod test of motor coordination. Old rats were injected daily with different doses of CCK-8S (0.32 to 8.0 microg/kg; IP) 10 min before the behavioral tests. Control groups included vehicle-injected old and adult (3-month-old) F 344 rats. To control for a possible development of tolerance to the behavioral effects of repeated CCK-8S administration, groups of aged rats were included which were subjected to an acute rather than a repeated CCK injection schedule. The repeated administration of CCK-8S did not influence the performance of the old rats in the hidden-platform version of the maze. In addition, the acute treatment with CCK-8S failed to modify navigation performance in this task, suggesting that drug-tolerance may not account for the lack of behavioral effects seen after repeated CCK-8S injection. During the "probe trial", the percentage of animals per group, which swam exactly across the former platform site, was markedly increased in aged rats treated repeatedly with 1.6 microg/kg CCK-8S. This might be indicative of improved retention of the prior platform location and/or a higher resistance of the learned escape response to extinction. The specificity of the effect of CCK-8S on processes related to spatial learning and memory is supported by the lack of effect on motor performance.

Age Factors↗

PubMed2001

Place aversion induced by microinjections of C-fragment of substance P into the dorsal periaqueductal gray of rats is mediated by tachykinin NK1 receptors.

Neural circuits in the dorsal periaqueductal gray matter (dPAG) play an important role in the integration of defensive behavior. The neurokinin substance P causes conditioned place aversion when administered into this region. The present study examined whether these effects may be mimicked by its carboxy-terminal amino acid sequence and whether they are influenced by prior treatment with the tachykinin NK1 receptor antagonist WIN51,708. The behavioral testing apparatus is a circular open field consisting of 4 uniform quadrants that are equally preferred by the rats prior to drug treatments. For conditioning, rats received drug injections on three consecutive days and were placed into their assigned quadrant. The carboxy-terminal analog (17.5 pmol/0.2 microl) applied into the dPAG produced place aversion effects with reduced time spent in the drug-paired quadrant on the testing day. The effects of the carboxy-terminal analog was antagonized by pretreatment with WIN51,708 (20 mg/kg, i.p.). Microinjection of WIN51,708 (20 mg/kg, i.p.), by its own, did not produce significant effects. These findings suggest that previous reports showing conditioned place aversion effects of SP injected into the dPAG are encoded by its carboxy-terminal sequence and due to its action on tachykinin NK1 receptors.

Androstanes↗

PubMed2000

Differential modulation of frontal cortex acetylcholine by injection of substance P into the nucleus basalis magnocellularis region in the freely-moving vs. the anesthetized preparation.

In vivo microdialysis was used to assess the effects of unilateral substance P (SP) injection into the nucleus basalis magnocellularis on extracellular levels of acetylcholine (ACh) in the frontal cortex, either in freely moving or urethane-anesthetized rats. The results show that the neurochemical effects of SP are critically dependent on the choice of the experimental preparation: In the freely-moving rat, the injection procedure led to behavioral and concurrent bilateral cholinergic activation in the frontal cortex. This cholinergic activation was ipsilaterally reduced by intrabasalis injection of SP (1 ng), indicating that the peptide exerted an inhibitory influence on the neurochemical effect exerted by handling, intracranial needle insertion, and vehicle injection. In the anesthetized preparation, SP had a biphasic dose-dependent action on cortical ACh: a short-lasting ipsilateral increase immediately after injection (especially with 1 ng), and a delayed bilateral increase after more than 2 h (10, 100 ng). The procedure of inserting the injection needle moderately increased cortical ACh levels. Methodologically, these data are discussed with respect to the importance of using anesthetized vs. freely moving rats and the effects of intraparenchymal injections.

Acetylcholine↗

PubMed2000

Auditory noise can prevent increased extracellular acetylcholine levels in the hippocampus in response to aversive stimulation.

The intent of this study was to investigate neurochemical and behavioural effects of aversive stimulation and the impact of auditory background noise. Using in vivo microdialysis, hippocampal acetylcholine was extracted and subjected to HPLC analysis while male Wistar rats were exposed to aversive stimulation similar to that used in conventional procedures for aversive conditioning. Three groups of animals were used. Animals in the first group were exposed to a single tone/footshock pairing followed by a tone alone 2 h later. Animals in the second group served as controls and were only exposed to the tone without shock. A third group was exposed to the same tone/shock pairing and tone as the first group while being exposed to constant background noise during the whole experiment. The results showed, that the tone/shock combination led to pronounced behavioral and cholinergic activation. In contrast, exposure to background noise prevented the increase in hippocampal ACh levels to tone/shock stimulation. The unconditioned behavioural response, however, was not prevented suggesting that hippocampal ACh is not a necessary correlate of behavioural activation or arousal. A second experiment intended to investigate the effects of background noise in a shuttle box avoidance learning paradigm where rats were trained to avoid an aversive footshock, which was signalled by a tone. There, one group of rats was exposed to background noise during avoidance learning, and the other group was not exposed to noise. Whereas both groups learned to avoid the shock to some degree over training, the noise exposed animals did not show improvement in escape performance over the course of training, indicating that the noise hindered development of an adaptive response to the shock. In summary, our data indicate that background noise can prevent increased extracellular hippocampal ACh levels in response to an aversive stimulus, and can also lead to deficits in learning to escape from shock.

Acetylcholine↗

PubMed2000

Superior water maze performance and increase in fear-related behavior in the endothelial nitric oxide synthase-deficient mouse together with monoamine changes in cerebellum and ventral striatum.

Nitric oxide (NO) has been implicated in the control of emotion, learning, and memory. We have examined endothelial NO synthase-deficient mice (eNOS-/-) in terms of habituation to an open field, elevated plus-maze behavior, Morris water maze performance, and changes in cerebral monoamines. In the open field, eNOS-/- animals were less active than wild-type controls but showed unimpaired habituation. In the plus-maze, an anxiogenic effect was observed. Proceeding from previous findings of deficits in hippocampal and neocortical long-term potentiation (LTP) in our eNOS-/- mice, we investigated whether these animals also express deficits in learning tasks that have been linked to hippocampal function and LTP. Unexpectedly, eNOS gene disruption led to accelerated place learning in the water maze. Furthermore, during long-term retention and reversal learning, eNOS-/- mice showed improved performance. In a cued version of the water maze task, eNOS-/- and control mice did not differ, implying that the superior performance of eNOS-/- animals on the former tasks cannot be attributed solely to differences in sensorimotor capacities. The neurochemical evaluation of the eNOS-/- mice revealed increases in the concentrations of the serotonin metabolite 5-HIAA in the cerebellum, together with an accelerated serotonin turnover in the frontal cortex. Furthermore, eNOS-/- mice had a higher dopamine turnover in the ventral striatum. These findings are discussed in terms of possible concomitant effects on physiological parameters, such as a decreased reactivity of GABAergic neurotransmission or changes in vascular functions, and effects on behavioral processes related to reinforcement, learning, and emotion.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Evidence for resistance to MPTP in C57BL/6 x BALB/c F1 hybrids as compared with their progenitor strains.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is capable of producing a syndrome in mice which shares major characteristics with human Parkinson's disease. There is evidence for a genetic influence on the degree of damage exerted by MPTP, since different strains of mice can dramatically differ in their response to MPTP. We produced reciprocal F1 hybrids by crossbreeding the MPTP-susceptible C57BL/6 strain with resistant BALB/c. These hybrids were compared to the parental strains using neural and behavioral measures in order to characterize the genetic transmission of MPTP-susceptibility. The F1 generation as a whole had a lower depletion of neostriatal dopamine levels than even found in BALB/c. Furthermore, there was no significant loss of tyrosine hydroxylase-positive cells in the substantia nigra and quick recovery from deficits in motor behavior in F1, herein resembling BALB/c. We suggest that several loci are involved in susceptibility to MPTP, and that the trait is under control of recessive susceptibility and/or dominant resistance alleles, which interact in F1, leading to extremely low susceptibility.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2000

Anxiolytic-like effects in rats produced by ventral pallidal injection of both N- and C-terminal fragments of substance P.

Prior studies have shown that the neurokinin substance P (SP) has anxiolytic-like effects when administered into the nucleus basalis (NB) area of the rat ventral pallidum. The present work was performed to examine whether the anxiolytic effects of SP in the nucleus basalis can be assigned its amino (N)- or carboxy (C)-terminal moiety. Using the elevated plus-maze model of anxiety in combination with unilateral injection of N-terminal SP(1-7) or C-terminal SP(7-11) into the NB region, we found that the treatment with either SP-fragment increased the number of entries into and time spent on the open arms as well as excursions into the end of the open arms, indicative of an anxiolytic-like profile. Furthermore, the effective doses of SP(1-7) (0.67 ng) and SP(7-11) (0.45 ng) were equimolar to the dosage of the whole SP molecule (1 ng), which was effective to reduce anxiety. Thus, the results support earlier findings that ventral pallidal injection of SP has anxiolytic-like effects and provide new evidence that fragments of SP, representing the N- and C-terminal domain of the peptide can reduce fear-parameters at a concentration similar to that of the parent peptide.

Animals↗

PubMed2000

Injections of tacrine and scopolamine into the nucleus accumbens: opposing effects of immediate vs delayed posttrial treatment on memory of an open field.

Using the paradigm of habituation learning in the open field, we tested the effects of microinjections of the nonspecific acetylcholine-esterase inhibitor tacrine (0.1, 1.0, 10.0 micrograms), and the muscarinic receptor antagonist scopolamine (0.1, 1.0, 10.0 micrograms) into the core of the nucleus accumbens. When injected immediately after the first exposure to the open field (posttrial), tacrine dose-dependently enhanced habituation of rearing behavior during the test on the following day, indicating a facilitation of memory. In contrast, scopolamine impaired habituation of rearing behavior at the two lower doses, but not at the highest dose. When scopolamine or tacrine (10.0 micrograms) was injected with a delay of 5 h after the learning trial, both drugs impaired habituation of rearing on the following day. The effects on locomotor activity differed from those on rearing behavior. Here, habituation on Day 2 was observed only in those animals which had received posttrial injections of vehicle or 10 micrograms of tacrine on the day before, whereas in animals which had received the two lower doses of tacrine, locomotor activity on Day 2 was not significantly decreased. In animals with posttrial treatment of scopolamine, locomotor activity on Day 2 was even enhanced, especially with the lower doses. No such effects were observed when scopolamine or tacrine (10.0 micrograms each) was injected with a delay of 5 h after the learning trial. These results show that cholinergic manipulations aimed at the nucleus accumbens can have substantial effects in this posttrial memory paradigm, which depend on drug, dose, and time of injection, and the specific kind of behavioral measure analyzed. Among others, the findings are discussed with respect to the role of muscarinic and nicotinergic cholinergic mechanisms in the nucleus accumbens on cognitive functions. They may be relevant, for example, for understanding the psychopathology of Alzheimer's disease, since the nucleus accumbens is one of the sites where cholinergic neurons are lost in this neurodegenerative disease.

Animals↗

PubMed2000

Measuring fear and anxiety in the marmoset (Callithrix penicillata) with a novel predator confrontation model: effects of diazepam.

This report describes a new experimental method for measuring fear and anxiety in Cerrado marmosets (Callithrix penicillata). In order to test the sensitivity of the behavioral parameters to an anxiolytic substance, the effects of the benzodiazepine diazepam on the anxiety measures were examined. The strategy was to use a naturally occurring stimulus known to elicit anxiety and fear in this species. A taxidermized predator (the wild cat Felis tigrina) was chosen as the stimulus to induce anxiety-related behaviors on the basis of a preceding study in which various stimuli were systematically compared in their effectiviness to induce fear responses. The apparatus consisted of three parallel arms of equal dimensions, joining two perpendicular arms at each end, thus comprising a figure eight-like or five-arm continuous rectangular maze. The wild-cat was placed outside of one corner of the maze's outer parallel arms. Each subject was submitted to six treatments given in random order: three drug sessions (diazepam 1, 2 and 3 mg/kg, i.m.), saline, sham (injection control), and a control session, involving neither manipulation nor injection. Subjects were placed into the back of the chamber, out of sight of the 'predator', 20 min after a treatment and given free access to the maze for 30 min. The behavioral repertoire was recorded via videocamera. The following behaviors were considered to be possible indices of emotionality relevant to exposure to the predator in the paradigm used: scratching, scent marking, exploration, frequency and time spent in each of 13 defined sections of the maze. Administration of diazepam induced a significant reduction in scratching and an increase in the time spent in the vicinity of the 'predator', as well as in the frequency of exploratory behaviors, indicative of an anxiolytic effect. Gender did not influence the effect of treatment. These results suggest that this new ethologically-based test may be a useful method for studying anxiety and fear-induced avoidance in non-human primates and for pre-clinical research on psychoactive drugs.

Animals↗

PubMed2000

Facilitation of learning and long-term ventral pallidal-cortical cholinergic activation by proteoglycan biglycan and chondroitin sulfate C.

We have shown previously in the rat that biglycan, a recently discovered chondroitin sulfate proteoglycan, has neurotrophic effects which are mediated by its chondroitin/dermatan sulfate chains. Here we report that biglycan has neurochemical effects when injected into the nucleus basalis magnocellularis of the ventral pallidum, a site of dense cholinergic cell bodies. The effects on the cholinergic output in the frontal cortex are long lasting, indicating profound neuroactive function akin to that expected of a long-acting hormone. Injected into the same area of the brain, as well as into the ventricles in behaviorally impaired old animals, we found that biglycan can improve learning and memory in several behavioral paradigms. Furthermore, we show that both the neurochemical effectiveness as well as the promotion of learning is carried not by the proteoglycan per se, but rather by its chondroitin sulfate moiety, thus, demonstrating for the first time memory-promoting and neuroactive effects of a glycosaminoglycan, namely, chondroitin sulfate C. The results suggest that biglycan and other extracellular matrix molecules can have neurobehavioral and pharmacological functions for beyond those traditionally attributed to this class of molecules.

Acetylcholine↗

PubMed2000

MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences.

To investigate the impact of strain and sex in the l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease, C57BL/6 and BALB/c mice were treated with either systemic MPTP-HCl (4 x 15 mg/kg) or saline and were examined in a number of behavioral tests. Furthermore, neostriatal and ventral striatal monoamine contents were determined, and the numbers of tyrosine hydroxylase-immunostained cells were counted in the substantia nigra and ventral tegmental area. Open-field testing showed that locomotor activity was drastically reduced as an acute effect of MPTP in both strains; however, subsequent recovery to control levels was faster in BALB/c mice than in C57BL/6. Nest building also indicated strain-dependent effects, since it was delayed only in C57BL/6 mice treated with MPTP. The other tests (grip test, pole test, rotarod, elevated plus-maze), although partly sensitive for over-all strain or gender differences, turned out not to be useful to compare MPTP effects in these two strains. Neurochemically, MPTP led to more severe neostriatal dopamine depletions in C57BL/6 (-85%) than in BALB/c mice (-58%). Histologically, a loss of tyrosine hydroxylase immunoreactivity (-25%) was observed only in the substantia nigra of C57BL/6 animals. Thus, our analysis consistently showed that the C57BL/6 mouse strain is more susceptible to MPTP than the BALB/c strain. Sex differences in MPTP sensitivity were not observed in our mice. The implications of these findings for the search for genes related to susceptibility to neurodegeneration are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2000

Substance P and its role in neural mechanisms governing learning, anxiety and functional recovery.

The neurokinin Substance P (SP) is widely distributed in the central nervous system and has been extensively studied in various functional aspects. This review focuses on the behavioral relevance of SP. Here we show that SP can have memory-promoting, reinforcing and anxiolytic-like effects when administered systemically or into the nucleus basalis of the ventral pallidum. These effects seem to be mediated via the SP-preferring NK(1)receptor and differentially related to N- versus C-terminal fragments of the undecapeptide. Secondly, SP injection into the ventral pallidum can lead to increases of acetylcholine in frontal cortex and dopamine in nucleus accumbens, suggesting that the hypermnestic, positively reinforcing and anxiolytic effects observed upon basal forebrain injection of SP are mediated by activation of the nucleus accumbens-ventral pallidum circuitry. Furthermore, SP and certain SP-fragments may not only be considered to have beneficial behavioral effects in normal animals, but can also prevent lesion-induced functional deficits and improve the speed of recovery. This indicates that SP agonists might also have a neuroprotective capacity in parallel with recovery-promoting actions.

Animals↗

PubMed2000

ACTH4-10, substance P, and dizolcipine (MK-801) accelerate functional recovery after hemilabyrinthectomy in goldfish.

In this study, we evaluated the goldfish model of hemilabyrinthectomy for investigating potential recovery-promoting drugs. In this lesion model, the unilateral removal of the labyrinth induces a postural imbalance in response to light (Dorsal Light Reflex), from which the animals can recover over time. The behavioral effects of two neuropeptides were tested--namely, of substance P and ACTH4-10, both of which are known to promote functional recovery in several other lesion models. Furthermore, the effect of MK-801, an antagonist of the glutamatergic NMDA-receptor subtype, was tested because this substance has also been shown to exert a neuroprotective effect. After lesion of the right labyrinth, the animals (n = 12) were treated intraperitoneally daily either with vehicle (n = 12), substance P (n = 11), ACTH4-10 (n = 12), or MK-801 (n = 12). Another group (n = 11), which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. The lesion group, treated post-operatively with vehicle, did not recover from the postural deviation over the 24-d testing period. In contrast, all three test substances accelerated the functional recovery after unilateral labyrinthectomy. The decrease of the dorsal light reflex persisted even after cessation of drug treatment after 20 d. The results indicate that using the dorsal light reflex in the model of hemilabyrinthectomy in goldfish provides a useful approach to studying the ability of potential new neurotrophic or neuroprotective drugs to promote functional recovery.

Adrenocorticotropic Hormone↗

PubMed1999

Post-trial administration of H1 histamine receptor blocker improves appetitive reversal learning and memory in goldfish, Carassius auratus.

Based on the hypothesis that neuronal histamine exerts an inhibitory influence on learning and reinforcement, goldfish were tested for post-trial effects of the H1 receptor blocker chlorpheniramine (CPA) on learning the location of a food source in one of two compartments, one black the other white, with a feeder located in each compartment. Testing was carried out over 6 days. On the training day a food pellet was placed into the feeder of one of the compartments. After consumption of the food the fish were injected i.p. with either vehicle or CPA either immediately after training or 3 h later. Twenty-four-hours later, food was placed in the same compartment and the time to begin feeding was recorded. On the next day the location of the food pellet was reversed, and testing was continued for 4 days. On the first test day the time to begin feeding was significantly longer for the vehicle injected fish as compared with those injected with CPA. The vehicle group also took longer to begin feeding than the CPA group on the first reversal test day. The results of the 3-h delay groups indicated no significant differences between vehicle and drug for any experimental session. These results suggest that post-trial blockade of the H1 histamine receptor can affect appetitive learning in goldfish either by improving long-term memory consolidation and/or by the additive reinforcing effects of CPA (known from previous studies) on behavior.

Animals↗