Intrahippocampal Administration Research Articles

Intrahippocampal NMDA Administration Alters Fos, Fos-Related Antigens, and Opioid Peptide Immunoreactivity and mRNA in Rats

In this study, the glutamate receptor agonist, NMDA, was used to induce epileptic seizures in order to compare the expression of the immediate early gene (IEG) products, Fos and Fos-related antigens (Fras), with the opioid peptides, dynorphin (DYN) and leu5-enkephalin (LE), in the rat hippocampus. Fos-ir and Fra-ir were observed in the dentate granule cells and nonpyramidal cells within the hippocampal formation at 1 h, and in all hippocampal cells and fields, 3 h following injection of NMDA into the ventral hippocampus. A detailed time-course analysis revealed a differential expression of Fos-ir and Fra-ir. In adjacent sections, a substantial decrease in DYN-ir and LE-ir in the mossy fibers occurred 1, 3, and 6 h after NMDA which was followed by a normalization or an elevation of the opioid peptides at later time points. Quantitative in situ hybridization histochemistry revealed that the hybridization signal representing c-fos mRNA was induced rapidly and transiently in hippocampal neurons. An increase in preproenkephalin (PPE) mRNA in the dentate granule cells was observed 1, 3, and 6 h after NMDA, with a peak at 6 h. Twenty-four and 48 h after NMDA, hybridization signals for PPE and preprodynorphin (PPD) were barely detectable. At 72 h, the level of PPD mRNA was not significantly different from control values. There is a different time course of expression for the Fos and Fra family of genes after in vivo NMDA. The significance of the results is discussed with regard to IEG regulation of opioid peptide gene expression.

Working memory deficits induced by intrahippocampal administration of 8-OH-DPAT, a 5-HT 1A receptor agonist, in the rat

In a test of working memory using a three-panel runway task, the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at 1.0 mg/kg i.p. significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel gates at four choice points), but it had no effect on errors in a test of reference memory. Intrahippocampal injection of 8-OH-DPAT at 10 μg/side also significantly increased the number of working memory errors, without affecting that of reference memory errors. The effect of intrahippocampal 8-OH-DPAT (10 μg/side) on working memory was blocked by the 5-HT 1A receptor antagonist, (−)-propranolol, at 5 mg/kg i.p. These results suggest that activation of hippocampal 5-HT 1A receptors impairs working memory, but does not affect retention of reference memory.

Dopaminergic modulation of pilocarpine-induced motor seizures in the rat: The role of hippocampal D 2 receptors

This study examined the role of hippocampal dopamine D 2 receptors in the genesis of limbic seizures induced by muscarinic agonists in the rat. Pilocarpine, 600 mg/kg, elicited rapid and usually fatal convulsions. These were not affected by focal injections of saline (1 μl) into both hippocampi. Pretreatment of the dorsal, but not the lateral hippocampus, with the D 2 agonist trans-(+)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H-pyrazolo-(3,4-g)quinoline hydrochloride (LY 171555, 2 μg per side), did not alter the frequency of pilocarpine-induced convulsions, but significantly delayed their appearance and reduced their intensity. LY 171555 similarly increased the latency of seizures induced by focal hippocampal injection of carbachol (100 μg), without changing the frequency or the severity. The selective D 2 antagonist raclopride, injected dorsally into both hippocampi dose-dependently facilitated motor seizures evoked by pilocarpine (100 mg/kg), the cholinomimetic at this dose being ineffective as a convulsant in saline-treated animals. Intrahippocampal administration of the D 1 agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 2 μg per side) did not facilitate pilocarpine seizures and did not potentiate the proconvulsant action of raclopride. These data demonstrate that activation of the dopaminergic system, via D 2 receptors in the dorsal hippocampus, is capable of protecting the animal against limbic motor seizures arising from excessive muscarinic stimulation of the hippocampus. Since the blockade of D 2 receptors in the hippocampus markedly lowered the seizure threshold to pilocarpine, this would suggest that the dopaminergic input to the hippocampus is normally tonically active and functions physiologically to prevent epileptogenesis.

In rats, the metabotropic glutamate receptor-triggered hippocampal neuronal damage is strain-dependent

The effect of intrahippocampal (i.h.) and intraocular (i.o.) administration of the selective metabotropic glutamate receptor (mGluR) agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S, 3R-ACPD) was studied in different rat strains. A massive hippocampal damage was observed in CD/SD and Fischer 344 but not in SD/Rij and Brown Norway rats 7 days following the i.h. injection of 1S, 3R-ACPD, while no retinal damage was observed following its i.o. administration. Moreover, 1S, 3R-ACPD reduced the N-methyl-D-aspartate (NMDA) toxicity in the retina of both CD/SD and SD/Rij rats. Regardless of its toxic action on hippocampal neurons the i.h. injection of 1S, 3R-ACPD caused an acute stimulation of motor activity in both CD/SD and SD/Rij rats. This effect was blocked by the intracerebroventricular (i.c.v.) administration of the putative mGluR antagonist L-2-amino-3-phosphono-propionic acid (L-AP3). It is suggested that the differential expression of mGluR subtypes might determine their role in brain pathology.

Regional effects of pertussis toxin in vivo and in vitro on GABA B receptor binding in rat brain

Agonist binding to GABA B receptors modulates the activity of the guanine nucleotide binding proteins, Go and Gi. These G proteins are ADP-ribosylated by pertussis toxin and this prevents them from coupling to the GABA B receptor resulting in a reduction in high-affinity GABA B binding. GTP, which binds to a different site on the G protein α subunit, also reduces the affinity of the receptor for the G protein, and this can be used as a “marker” for G protein-GABA B receptor linkage. We have examined GABA B binding site distribution in rat brain after unilateral intrahippocampal pertussis toxin injection in vivo, and after incubating brain slices in pertussis toxin in vitro, using the technique of receptor autoradiography. The effect of pertussis toxin was compared with that of GTPγS on GABA B binding. Intrahippocampal pertussis toxin administration reduced GABA B but not GABA A receptor binding and the effects appeared to be limited by pertussis toxin diffusion. More widespread reductions in GABA B binding were seen after incubation of brain slices in vitro but the extent varied in different brain regions. No reduction was detected in the corpus striatum. GABA B binding was also reduced in membranes prepared from cerebral cortex, hippocampus and cerebellum but there was no sigificant reduction in the corpus striatum after pertussis toxin treatment. GTPγS reduced GABA B binding to a similar extent in all areas studied irrespective of their sensitivity to pertussis toxin suggesting that while GABA B binding sites are linked to G proteins throughout the rat brain, those in the corpus striatum may be predominantly pertussis toxin insensitive.

Stimulation of 5-HT 1A receptors in the dorsal hippocampus impairs acquisition and performance of a spatial task in a water maze

8-Hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), a potent 5-HT 1A receptor agonist, was infused in the dorsal hippocampus of rats and its effect on acquisition and performance of a 2-platform spatial discrimination task was studied using a water maze. The infusion (0.5 μl/min) of 2 but not 0.4 μg 8-OH-DPAT in the CA1 region of the dorsal hippocampus impaired rats' accuracy with no effect on latency (except day 3). At 5 μg 8-OH-DPAT impaired rats' accuracy and significantly increased choice latencies from day 2 to day 5 of the training period. The dose of 2 μg significantly increased the errors of omissions on the first day of training and animals which had received 5 μg 8-OH-DPAT made significantly more errors of omission on the first and second days of training. Intrahippocampal administration of 1 μg spiroxatrine, a 5-HT 1A receptor antagonist, antagonized the effect of 5 μg 8-OH-DPAT on accuracy and choice latency with no significant effect on the errors of omission on days 1 and 2 of training. Infusion of 2 and 5 μg 8-OH-DPAT in the dorsal hippocampus also impaired accuracy in well-trained rats. The results suggest that stimulation of 5-HT 1A receptors in the CA1 region of the dorsal hippocampus causes an impairment of spatial discrimination in rats.

Administration of quinolic acid in the rat hippocampus induces expression of c- fos and NGFI-A

We have studied the effect of intrahippocampal administration of quinolinic acid (QUIN) on the temporal expression of mRNAs encoding the immediate early genes (IEGs) c- fos and NGFI-A, by in situ hybridization histochemistry. After administration of QUIN to the left hippocampus, expression of mRNA of both IEGs was transiently stimulated. Maximal expression was found between 1 and 3 h. mRNA of both IEGs was simultaneously expressed in the ipsilateral and contralateral sides in the granule cell layer of the dentate gyrus, the pyramidal cell layer of the CA1 and CA3 fields as well as in the cortex. After pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg i.p. − 30 min) the increased expression of both IEGs was partially prevented in the hippocampus and completely in the cortex. No inhibition was observed after treatment with the AMPA antagonist NBQX (30 mg/kg i.p. −15, −5 and +10 min). Additional delayed expression of both IEGs was observed in the ipsilateral hippocampus. This expression was related to cell damage. Twelve h after QUIN administration, c- fos and NGFI-A mRNAs were present in the dentate gyrus. After 4 days, only c- fos mRNA was observed in the dentate gyrus and CA1 field while no NGFI-A mRNA was detected. The present results show that the effect of QUIN is mediated by NMDA and not by AMPA receptors.

NMDA receptor antagonists protect against seizures and wet-dog shakes induced by 4-aminopyridine

The effect of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on the generalized tonic-clonic convulsions and wet-dog shakes induced by the intraperitoneal (i.p.) or the intrahippocampal (i.h., stereotaxic microinjection into the CA1 region) administration of 4 amirsopyridine (4-AP)was studied in rats. Pretreatment with NMDA competitive and non-competitive antagonists resulted in potent protection against the motor effects of both the i.p. and the i.h. administration of 4-AP. MK-801 (0.25 mg/kg i.p.) and 3-(2-carboxypipcrazin-4-yl)propyl-1-phosphonic acid (CPP, 0.8 nmol intracerebroventricular. i.c.v.) showed the most powerful anticonvulsive effect, since they prevented the occurrence of generalized tonic convulsions and the death of the animals in convulsions after i.p. 4-AP. The i.c.v. injection (10 nmol) of the NMDA competitive antagonists 2-amino-5-phosphonopentanoate (AP-5) and 2-amino-5-phosphonoheptanoate (AP-7) also showed a clear though less potent protective effect. Similarly, the frequency of wet-dog shakes induced by i.h. 4-AP was markedly decreased by pretreating the animals with i.p. MK-801 or with i.c.v. CPP or AP-7. However, the co-injection of CPP with 4-AP failed to protect against the occurrence of wet-dog shakes. The i.c.v. pretreatment with the unselective antagonist, kynurenate (up to 68 nmol) or with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxalinc-2,3-dione (0.5 nmol), did not significantly modify the effects of 4-AP when administered either i.p. or i.h. We conclude that NMDA receptors arc involved in the mechanism of the convulsive activity induced by 4-AP, probably because this drug induces the release of glutamate.

Neurotransmitter receptors involved in post-training memory processing by the amygdala, medial septum, and hippocampus of the rat

Rats were trained and tested in habituation to a novel environment and step-down inhibitory avoidance. Immediately after training in each task the animals received intra-amygdala, intraseptal, or intrahippocampal micro-injections of agonists and antagonists of various neurotransmitter receptors. In the habitation task, intrahippocampal, but not intra-amygdala or intraseptal administration of the NMDA receptor antagonist aminophosphornopentanoic acid (AP5, 5.0 micrograms) or of the muscarinic receptor antagonist, scopolamine (2.0 micrograms) caused amnesia and the indirect antagonist of GABA-A receptors, picrotoxin (0.08 microgram), caused retrograde facilitation. Intrahippocampal administration of the respective agonists, glutamate, oxotremorine, and muscimol, had effects of their own opposite to those of the blockers, and norepinephrine (0.3 microgram) caused memory facilitation. In the avoidance task, results obtained with drug infusions given into the three structures were very similar: in all cases, AP5, scopolamine, and muscimol were amnestic, and glutamate, oxotremorine, norepinephrine, and picrotoxin caused memory facilitation. In addition, also in the three structures, picrotoxin counteracted the amnestic effect of AP5 and/or scopolamine and the beta-adrenoceptor blocker, timolol (0.3 microgram), while ineffective on its own, attenuated all the effects of picrotoxin. The results suggest that similar synaptic mechanisms in the amygdala, medial septum, and hippocampus are involved in memory consolidation: NMDA, muscarinic, and beta-noradrenergic receptors stimulate and GABA-A receptors inhibit this process, and beta-noradrenergic receptors modulate the GABAergic synapses. In the avoidance task these mechanisms operate in the three structures: in habituation only those in the hippocampus are operative. Possibly in each structure these mechanisms regulate, if not actually consolidate, a different aspect, component, or form of memory.

In vivo modulation of N-methyl- d- aspartate receptor-dependent long-term potentiation by the glycine modulatory site

The role of the glycine modulatory site in N-methyl- d-aspartic receptor function was examined by determining the effect of the glycine site antagonist, 7-chlorokynurenic acid, on the induction of long-term potentiation at the commissural-CA1 synapse in anesthetized rats. Robust long-term potentiation of population excitatory postsynaptic potentials and population spike responses recorded extracellularly in the stratum pyramidale and in stratum radiatum of CA1 developed after high frequency stimulation (100 Hz for 1 s) of commissural fibers during continuous intrahippocampal administration of vehicle solution (0.15 M NaCl). In contrast, infusion of either 7-chlorokynurenic acid (400 μM) or of the N-methyl- d-aspartic receptor antagonist, d-2-amino-5-phosphonovaleric acid (100 μM), significantly attenuated or completely blocked the development of long-term potentiation. When 7-chlorokynurenic acid was infused together with the glycine analog, d-serine (1 mM), long-term potentiation developed that was comparable to that observed in control animals. Intrahippocampal administration of d-serine alone was associated with slightly greater magnitude of long-term potentiation than observed in control animals. Collectively, these findings establish that in intact hippocampus, activity at the glycine modulatory site is necessary for activation of the N-methyl- d-aspartic receptor complex. Furthermore, these results suggest that the glycine modulatory site may not be fully saturated in vivo, and thus can serve to regulate N-methyl- d-aspartate receptor function.

Convulsions and wet-dog shakes produced by systemic or intrahippocampal administration of ruthenium red in the rat

In this work we have studied in the rat the behavioral effects of the intraperitoneal (i.p.) and intrahippocampal (i.h.) administration of ruthenium red (RuR), an inorganic dye which has been shown to inhibit neurotransmitter release in synaptosomes. The i.p. injection induced initially flaccid paralysis and subsequently generalized tonic-clonic convulsions. It contrast, unilateral RuR microinjection into the CA1 area of the hippocampus produced complex seizure behavior and wet-dog shakes (WDS). The i.p. administration of the serotonin receptor antagonist ketanserin markedly inhibited the WDS induced by i.h. RuR. In contrast, the i.h. injection of ketanserin and of the gamma-aminobutyric acid (GABA) agonists 4,5,6,7-tetrahydroisoxazol[5,4-c]pyridin-3-ol(THIP) and baclofen together with RuR did not affect the frequency of WDS nor the seizure behavior. However, the i.h. injection of the GABA uptake blocker nipecotic acid, simultaneously with RuR, increased the frequency of WDS. The release of [3H]GABA, measured in synaptosomes of different cerebral structures of the rats injected i.p. with RuR, and in slices of the CA1 area after i.h. injection of the dye, was not affected. Histological observations of the injected area showed a specific and intense staining of the somas of the CA1 pyramidal neurons. It is concluded that the convulsant action induced by i.h. RuR microinjection is probably the result of an increased excitability of these CA1 neurons, which is independent of any action on GABA release.

Effects of unilateral intrahippocampal injection of MK-801 upon local cerebral glucose utilisation in conscious rats

The effects of unilateral intrahippocampal injections of the non-competitive NMDA receptor antagonist, MK-801, on local cerebral glucose utilisation have been examined in conscious rats using [14C]2-deoxyglucose autoradiography. The intrahippocampal injection of MK-801 (10 nmol) induced significant marked increases in glucose use in the ipsilateral hippocampus molecular layer and dentate gyrus (by 31 and 44%, respectively). Function-related glucose use in brain regions with known neuronal connections with the site of drug administration (e.g. enthorhinal cortex, septal nucleus, mamillary body) was minimally altered after intrahippocampal MK-801 administration. Blockade of hippocampal NMDA receptors does not appear to modify activity, as reflected in local glucose utilisation, in hippocampal afferent and efferent circuits in conscious rats.

Substantia nigra-mediated anticonvulsant action: a possible role of a dopaminergic component

A number of neural pathways may mediate nigral control of epilepsy. According to the literature, a GABAergic nigrotectal pathway may be responsible for the control exerted by the substantia nigra on the diffusion of discharges toward spinal targets, while the nigrothalamic Projection may transfer nigral influence on premotor neocortical epilepsy. Since there is probably an anatomical nigrohippocampal pathway arising from dopaminergic cells in the substantia nigra, we tested the effects of stimulating the substantia nigra pars compacta (SNpc) on focal hippocampal epilepsy induced by penicillin injection in the cat. The possibility of dopamine involvement was further tested by studying the effects of intraperitoneal injection of haloperidol, a dopamine receptor blocking agent on nigrohippocampal influences, while to verify the precise site of action, in other groups of cats, sulpiride and apomorphine (D-receptor antagonist and agonist, respectively) were locally administered in the dorsal hippocampus. Furthermore, modifications of hippocampal epileptiform EEG were studied in control conditions and following SNpc electrolytic lesions. Results showed a strong nigral suppressive effect on focal hippocampal epilepsy. Nigral stimulation induced a significant decrease in both frequency and amplitude of hippocampal spikes, which disappeared either about 10 min after i.p. injection of haloperidol 1 mg/kg or about 5 min after intrahippocampal administration of sulpiride, and did not return during a further hour or more of experimental observation. It should be emphasized that in the absence of nigral stimulatiion, both haloperidol and sulpiride dis not modify hippocampal spike frequency. Apomorphine application to dorsal hippocampus induced a marked reduction of hippocampal epileptiform activity parallel to the effect observed during SNpc stimulation. On the other hand, in SNpc-lesioned cats a certain degree of spiking enhancement was observed in hippocampal recordings. The experimental findings are regarded as evidence that the SNpc is able to control hippocampal-based epileptiform spikes and that this influence is dopaminergic in nature. The substantia nigra thus appears to have multiple elective influences, in different brain loci, on epileptic phenomena by selective activation of its different efferent projections, involving both GABAergic and dopaminergic systems.

Cis-(+)-8-OH-1-CH3-DPAT, (+)ALK-3, a novel stereoselective pharmacological probe for characterizing 5-HT release-controlling 5-HT1A autoreceptors

The somatodendritic 5-HT1A autoreceptor regulating 5-HT neuronal activity is currently poorly defined pharmacologically because there are no specific antagonists, but also because potent and stereoselective agonists are scarce. Moreover, there have been few, if any, attempts to specifically investigate structure-activity relationships for agonists acting at this site. Employing brain microdialysis techniques, we have examined the effects of the enantiomers of cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (ALK-3; 0.01-0.3 mg/kg s.c.), its trans-1-methyl analogue (ALK-4; 0.3 mg/kg s.c.) and the pure enantiomers of the parent compound--8-OH-DPAT (0.3 mg/kg s.c.)--in an attempt to address stereochemical agonist structure-activity requirements of 5-HT release-controlling 5-HT1A autoreceptors in brain. The cis-1-methylated 8-OH-DPAT analogue (+)ALK-3 was comparable to the parent compound in reducing the 5-HT output from rat ventral hippocampus. In comparison, both (-)ALK-3 and the racemic trans-diastereomer to ALK-3, ALK-4, were inactive, while the two stereoisomers of 8-OH-DPAT strongly reduced 5-HT release. Pretreatment with (-)pindolol (8 mg/kg s.c.), which has high affinity for 5-HT1A radioligand binding sites, blocked the reduction of hippocampal 5-HT release induced by a submaximally effective dose of (+)ALK-3. The direct intrahippocampal administration of (+)ALK-3 (10 microM) via the perfusion medium did not affect 5-HT output. In summary, the data indicate that (+)ALK-3, like 8-OH-DPAT, is a very potent 5-HT receptor agonist which inhibits terminal 5-HT release in rat hippocampus, probably via activation of somatodendritic 5-HT1A autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

GABAergic neurons are spared after intrahippocampal kainate in the rat

The present study used Nissl stains and glutamate decarboxylase immunoreactivity (GAD-IR) to quantify the acute and chronic toxicity of kainic acid (KA) on focal and remote hippocampal principal neurons (i.e., pyramidal and granule cells) and on putative inhibitory neurons (GAD-IR or GABAergic) following intrahippocampal KA administration. Concentrations of 0.5, 1.0, 1.25 or 1.5 μg KA/0.2 μl were injected unilaterally into the posterior hippocampus of rats ( n = 32), with survival periods of 1, 3, 5, 14, 21, 30 and 60 days. The age-matched control animals ( n = 10) received an intrahippocampal injection of 0.2 μl saline (sham control, n = 4) or no injection (normal, n = 6). The ipsilateral (KA +) cell counts demonstrated a selective vulnerability of CA 3 and CA 4 pyramidal neurons which was maximal at 14 days and unchanged to 60 days. However, in the same region, putative inhibitory (GAD-IR) neurons were resistant to the neurotoxic effects of KA. Contralateral (KA −) pyramidal cell and GAD-IR neuron densities were equivalent to controls. The present data demonstrate a selective resistance to KA by GABA neurons compared to the vulnerability of pyramidal neurons. Because GABA neurons are relatively spared in the KA focus, loss of GABAergic inhibitory neurons is probably not a mechanism for the seizure sensitivity in the KA model.

The influence of antidepressive treatment on GABA-related mechanisms in the rat hippocampus: Behavioral studies

The effect of antidepressive treatment upon central GABAergic mechanisms has been studied in a behavioral model. Local injections (denate gyrus of the dorsal hippocampus) of picroxin, a chloride channel blocker linked with the function of GABA-A receptor complex, potently stimulated rat motility recorded in the automated open fields. The intra-hippocampal administration of GABA antagonized the behavioral effect of picrotoxin (0.5 μg). Similar effects were produced by addition to picrotoxin solution (0.25 μg) of the GABA-A receptor agonist muscimol (0.25 μg). Chronic (21-day), but not single, treatment of rats with desipramine (10 mg/kg, IP, daily) significantly attenuated picrotoxin-induced locomotor stimulation, when the GABA antagonist was given 24 hr after the last dose of the antidepressant. Repeated electroconvulsive shocks did not significantly change picrotoxin effect, while single shock produced some degree of inhibition of drug-induced motor stimulation. It is hypothesized that chronically applied desipramine, but not electroconvulsive shocks, may enhance the activity of hippocampal GABA-A receptor-related system.

Effects of intrahippocampal administration of colchicine on incentive contrast and on radial maze performance.

Effects of intrahippocampal administration of colchicine on incentive contrast and on radial maze performance.

Effects of intrahippocampal administration of colchicine on incentive contrast and on radial maze performance.

The behavior of rats given intradentate injections of the neurotoxin colchicine was examined in three experimental settings. In Experiment 1, colchicine-treated, artificial cerebrospinal fluid (CSF)-treated, and untreated animals did not differ in the intake of 32% and 4% sucrose solutions, nor did they differ in degree of successive negative contrast when the 32% solution was changed to 4% sucrose. In Experiment 2, the colchicine-treated and CSF-treated animals did not differ in degree of suppression in the intake of a 0.15% saccharin solution when it preceded 32% sucrose in once-daily pairings (anticipatory contrast), nor did they differ in reversal performance when saccharin-sucrose and saccharin-saccharin pairings were reversed. In Experiment 3, the colchicine-treated animals were substantially impaired in radial-arm maze performance compared with CSF-treated controls. These results suggest that a completely functioning hippocampus is not necessary for the memory of reward quality, the comparison of rewards, the suppression of behavior when reward is decreased, the formation of associations between two levels of reward, and the reversal of this association, as long as these processes are reflected in consummatory behavior. The data are interpreted in terms of differences between instrumental behavior and sensory memory and/or consummatory behavior--an interpretation that is not incompatible with a deficiency in working memory in the animals with lesions.

Effects of intrahippocampal injections of the cholinergic neurotoxin AF64A on open-field activity and avoidance learning in the rat

The effects of direct intrahippocampal administration of the cholinergic neurotoxin, AF64A, were investigated in male rats. Bilateral injections of AF64A (5 nmole/2 microliters) produced a significant decrease in choline acetyltransferase (CAT) activity in the dorsal hippocampus (25%) and overlying frontoparietal cortex (30%) but no changes in the striatum. Rats lesioned with AF64A exhibited increased levels of open-field activity, which was most marked at 1 week after the lesion; however, the rates of intrasession habituation were similar in lesioned and control rats. Lesioned rats also displayed deficits in acquisition and retention of a passive avoidance task and less dramatic deficits in acquisition of two-way shuttle box avoidance. These findings indicate that lesioning of cholinergic terminals in the hippocampus and/or cerebral cortex with AF64A leads to long-term deficits in learning and memory as well as increases in open-field activity.

海馬内gabaculine注入による扁桃核キンドリング発作の抑制効果

海馬内gabaculine注入による扁桃核キンドリング発作の抑制効果