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C A Marsden

Publications and source records attributed to C A Marsden.

At least 19 recordsLinked to original sources
PubMed2000

Strain differences to the effects of aversive frequency ultrasound on behaviour and brain topography of c-fos expression in the rat.

Previous studies have shown that ultrasound at 20 kHz produces an escape (defence) response in the hooded Lister rat. This study compares the ultrasound-induced behavioural response in the hooded Lister and albino Wistar rat. Ultrasound (continuous tone, square wave, 20 kHz) produced an initial characteristic startle response (brisk running) in the hooded Lister rat that was followed immediately after cessation of the ultrasound by a period of freezing behaviour. In contrast, Wistar rats showed no initial escape response but a prolonged period of freezing that started during the ultrasound and continued for a period after the end of the ultrasound. Immunohistochemical assessment of c-fos expression also showed a difference between the two strains with preferential expression in the dorsal region of the rostral and caudal periaqueductal grey (PAG) in the hooded Lister rat, while the expression occurred in the ventral PAG in the Wistar rats. In summary, the two strains exhibit distinct defensive behaviours and patterns of neuronal activation in response to the same aversive signal. It remains to be determined whether these differences relate to neuronal circuitry or perception of the signal, but analysis of the mechanisms involved may help our understanding of the heterogeneity of anxiety disorders.

Animals↗
PubMed2000

Cannabinoid receptors and reward in the rat: a conditioned place preference study.

RATIONALE: We wished to investigate further the hypothesis of an endogenous cannabinoid 'aversive counter-rewarding system, as the rewarding properties of cannabinoids using standard procedures remain ambiguous. OBJECTIVES: The purpose of this study was to confirm the behavioural effects of a highly potent synthetic cannabinoid agonist (HU210) and the selective cannabinoid antagonist SR 141716A using conditioned place preference (CPP). METHODS: HU210 (20, 60 and 100 microg kg(-1), SR141716A (0.25, 0.5, 2 and 3 mg kg(-1)), cocaine (15 mg kg(-1) and delta9-THC (1.5 mg kg(-1)) were given to male Lister hooded rats using an unbiased CPP design. RESULTS: SR141716A and cocaine produced place preference at all doses tested, whereas HU210 and delta9-THC produced aversion as expressed by time spent in the drug-paired compartment of the CPP apparatus. CONCLUSIONS: The aversive effects of cannabinoid agonists and the rewarding effect of the cannabinoid antagonist are suggestive of a cannabinergic tone in the rat brain. Further research is needed to determine the precise relationship of that tone with the reward pathways of the brain.

Animals↗
PubMed2000

Acoustically elicited behaviours in Lister hooded and Wistar rats.

It has been reported previously that experimenter-presented 20-kHz tones at low intensities produce bursts of locomotor running in Lister hooded rats, but reduced locomotion (freezing) in Wistar rats. Because rats emit 20-kHz tones when stressed, it was proposed that this ultrasound-elicited running and freezing behaviour in Lister hooded and Wistar rats, respectively, represents a model for qualitative strain differences in fear behaviour. The present studies examined the acoustic specificity of acoustically elicited locomotor behaviours in Lister hooded and Wistar rats. In Experiment 1, it was found that brief exposure (i.e., 15 s) of Lister hooded rats to tones at frequencies of 7, 12, or 20 kHz and intensities of 85-95 dB SPL, elicited running behaviour characterised by brief bursts of locomotion followed by periods of quiescence. Somewhat surprisingly, the 7- and 12-kHz tones elicited running behaviour at lower intensities than did the 20-kHz tones. In Experiment 2, it was found that exposure of Lister hooded rats to the 20-kHz acoustic stimulus (91-101 dB, SPL) for a much longer duration, up to 9 min, resulted in episodic bursts of locomotion and convulsions in a significant proportion of subjects. Both the maximal velocity of locomotion and the likelihood of occurrence of convulsions was related to the intensity of the acoustic stimulus. Exposure of Lister hooded rats to white noise for up to 9 min also elicited episodic bursts of locomotion and convulsions in an intensity-dependent manner. The white noise stimulus was found to be a more effective stimulus than the 20-kHz stimulus in this regard. In Experiment 3, it was found that Lister hooded rats exhibited reduced locomotion when they were exposed to a low-intensity 20-kHz acoustic stimulus (e.g., 81 dB, SPL). In Experiment 4, it was found that Wistar rats did not exhibit locomotor bursts or convulsions when presented with 20-kHz tones using stimulus parameters equal to and even greater than those that had been shown to be effective in producing locomotor bursts in Lister hooded rats. Rather, Wistar rats exhibited only reduced locomotion. The present data indicate that (1) running behaviour in Lister hooded rats is not specific for the 20-kHz stimulus. Moreover, (2) when compared to Lister hooded rats, Wistar rats are relatively insensitive to the running and convulsions elicited by acoustic stimuli. Finally, (3) both Lister hooded and Wistar rats exhibited reduced locomotion when presented with the 20-kHz tones, although the range of stimulus intensities that produces freezing behaviour is much more limited in Lister hooded rats because of their propensity to exhibit locomotor bursting and convulsions. Thus, it appears that the difference between the two strains with respect to their unconditioned locomotor responses to novel acoustic stimuli relates to the fact that Lister hooded rats are uniquely susceptible to acoustically elicited locomotor bursts and/or convulsions.

Acoustic Stimulation↗
PubMed2000

Lack of response suppression follows repeated ventral tegmental cannabinoid administration: an in vitro electrophysiological study.

Cannabinoid compounds have been reported to excite ventral tegmental neurons through activation of cannabinoid CB1 receptors. More recently, biochemical and whole-cell voltage-clamp studies carried out on CB1-transfected AtT20 cells have shown a rapid desensitization of these receptors following activation of protein kinase C by 4-alpha-phorbol. To investigate the possible physiological correlates of this phenomenon, we have studied the effects of repeated cannabinoid treatment on ventral tegmental area dopaminergic neuronal firing in vitro. Rat brain slices containing the ventral tegmental area were used for single-unit extracellular recordings. Only neurons meeting established electrophysiological and pharmacological criteria for dopaminergic neurons were used in the study (firing neurons were detected either using tungsten or glass microelectrodes). The high-affinity cannabinoid agonist HU210 produced a concentration-dependent increase in firing (1-15 microM; EC(50) approximately 7 microM). Initial HU210 exposure produced a significant increase in cell firing rate in the ventral tegmental area, with a maximum approximately 3.5-fold increase over pre-drug basal firing; a subsequent exposure to HU210 produced an approximately threefold increase over basal firing. Nevertheless, the duration and onset of excitation produced by the cannabinoid differed significantly between the first and second exposures; the first excitation lasted significantly longer than the second and required less time to reach a comparable change in firing rate. The increases in firing rate and the time to return to basal firing were not significantly different between exposures. Furthermore, the cannabinoid antagonist SR141716A completely prevented the HU210-induced excitation whilst having no effect on its own, thus indicating a CB1-receptor mediated mechanism for the observed increase in firing. Ventral tegmental area neurons are also excited by the GABA(A) receptor antagonist bicuculline. To assess the role of GABA in cannabinoid-mediated excitation, HU210 was added in the presence of bicuculline. HU210 did not affect the initial bicuculline-induced increase in firing, suggesting different sites of action for the two compounds. Our data fail to support previously reported findings using repeated cannabinoid administration and cell preparations. The maintained increase in DA drive elicited by the potent cannabinoid agonist HU210 in the in vitro ventral tegmental circuit could explain some of the behavioural properties of cannabinoids, such as the lack of tolerance for the psychotropic effects of marijuana seen in human users.

Action Potentials↗
PubMed1999

Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats.

Isolation rearing of rat pups from weaning produces neurochemical and behavioural changes that may have relevance to the neurodevelopmental basis of neuropsychiatric disorders such as schizophrenia. Although limited, studies have begun to probe for neuroanatomical changes produced by isolation rearing. In the present study, rat pups were reared in isolation, i.e., housed one per cage, from weaning. After 8 weeks of isolation, 'isolates' were compared to their socially reared controls (housed three per cage) in two behavioural paradigms: locomotor activity in a novel open field and prepulse inhibition (PPI) of the acoustic startle response. Subsequently, all rats were sacrificed and their brains removed. The hippocampus was sectioned and analysed immunohistochemically using an antibody to the synapse-specific protein synaptophysin, to gain an estimate of the synaptic content of selected hippocampal subfields. Isolates demonstrated locomotor hyperactivity and deficits in PPI relative to socially reared controls. Analysis of synaptophysin immunoreactivity suggested that isolates had significantly reduced synaptic content in the hippocampal dentate gyrus molecular layer, with smaller, non-significant reductions in the CA1 and CA3 regions. This pattern of change may be consistent with reduced neuronal input to the dentate gyrus via the entorhinal cortex, suggesting developmental changes in hippocampal-cortical circuitry. These preliminary studies extend the characterisation of isolation rearing as a model for the investigation of neurodevelopmental diseases such as schizophrenia.

Animals↗
PubMed1999

Modification of 5-HT2 receptor mediated behaviour in the rat by oleamide and the role of cannabinoid receptors.

Oleamide (cis-9,10-octadecenoamide) is an endogenous brain lipid which has been suggested to induce sleep in experimental animals. The mechanism of action is unclear but shares many of the characteristics of endogenous cannabinoids such as anandamide and has been shown to enhance in vitro responses to 5-HT and GABA. In the present study we investigated the effects of oleamide on two motor behaviours, back muscle contractions (BMC) and wet-dog shakes (WDS) induced in rats by treatment with the 5-HT2 receptor agonist DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride). We then examined the potential involvement of CB1 cannabinoid receptors in the responses to oleamide and the mechanism of interaction between CB1 and 5-HT2 receptors. Oleamide and the cannabinoid receptor agonist HU210 (6aR)-trans-3-(1,1-dimethylheptyl)6a,7,10,10a-tetrahydro-1-h ydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol) produced a hypolocomotion which was prevented by the CB1 antagonist SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride). Despite having no effect alone, oleamide and HU210 potentiated BMC induced by treatment with DOI. SR141716A alone did not affect the response to DOI but it blocked the potentiations caused by oleamide or HU210. WDS were unaffected by oleamide and slightly reduced by HU210. In vitro, oleamide and HU210 enhanced the high affinity binding of 5-HT to 5-HT2 receptors on rat cerebral cortex membranes labelled with 3H-ketanserin. Neither agent, however, altered 5-HT-stimulated phosphoinositide hydrolysis in rat cerebral cortex slices. Oleamide occupied CB1 cannabinoid receptors on rat brain membranes labelled with 3H-CP55940 with an IC50 of 10 microM. The data presented are consistent with oleamide acting via a cannabinoid recognition site to enhance 5-HT2 receptor function in vivo. The mechanism of the modulation is still unclear but it does not appear to involve a potentiation of 5-HT2 receptor-stimulated phosphoinositide hydrolysis.

Amphetamines↗
PubMed1999

Role of cholecystokinin type B receptors in ultrasound induced behavior in rats.

The cholecystokinin-tetrapeptide (CCK-4) can induce panic attacks in humans. The present study investigates the effects of CCK-4 and the CCK-B receptor antagonist L-365.260 on ultrasound induced defense behavior in the rat that may model the unconditioned aspects of panic behavior in man. CCK-4 (50 microg/kg) increased the defense response induced by ultrasound (95 dB) an effect prevented by pretreatment with L-365.260 (10 microg/kg). Compared with other antipanic/panicogenic drugs the effects of CCK-4 and L-365.260 were relatively small. In conclusion, drugs acting at the CCK-B receptor appear to have only a minor role in the modulation of an unconditioned aversive response.

Animals↗
PubMed1999

Investigation of stretching behaviour induced by the selective 5-HT6 receptor antagonist, Ro 04-6790, in rats.

1. The present study examined the effects of the selective 5-HT6 receptor antagonist 4-amino-N-(2, 6 bis-methylamino-pyrimidin-4-yl)-benzene sulphonamide (Ro 04-6790) on locomotor activity and unconditioned behaviour in male Sprague Dawley rats (230-300 g). 2. In non-quantified behavioural observations, animals treated with Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p) showed no overt behavioural signs except a dose-dependent reduction in locomotor activity and a behavioural syndrome of stretching, yawning and chewing. The latter behaviour was most pronounced between 30 and 90 min following the administration of Ro 04-6790. 3. Detailed analysis of the stretching and yawning behaviour showed that Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p.) dose-dependently induced stretching. The number of stretches observed following treatment with either Ro 04-6790 (10 mg kg(-1) i.p.) or Ro-04-6790 (30 mg kg(-1), i.p.) was significantly greater than that observed in saline-treated rats. The yawning behaviour, however, was not dose-dependent nor was the number of yawns in any of the drug treated groups significantly greater than in those treated with saline. 4. Pretreatment (30 min) with the non-selective muscarinic antagonists scopolamine (0.1, 0.3 or 1 mg kg(-1), i.p.) and atropine (0.3, 1 or 3 mg kg(-1), s.c.) but not methylatropine (1, 3 or 10 mg kg(-1), s.c) significantly inhibited stretching induced by Ro 04-6790 (30 mg kg(-1), i.p.). 5. The dopamine D2-like receptor antagonist, haloperidol (0.03, 0.1 or 0.3 mg kg(-1), s.c.) given at the same time as Ro 04-6790 (30 mg kg(-1), i.p.) had no effect on the stretching induced by the 5-HT6 antagonist. 6. These data suggest that systemic injection of the 5-HT6 antagonist, Ro 04-6790, produces a stretching behaviour that appears to be mediated by an increase in cholinergic neurotransmission in the CNS and which could be a useful functional correlate for 5-HT6 receptor blockade. There is no evidence for dopamine D2-like receptor involvement in this behaviour.

Acetylcholine↗
PubMed1999

Pindolol-insensitive [3H]-5-hydroxytryptamine binding in the rat hypothalamus; identity with 5-hydroxytryptamine7 receptors.

Pindolol-insensitive [3H]-5-hydroxytryptamine ([3H]-5-HT) binding to rat hypothalamic membranes was pharmacologically and functionally characterized to resolve whether this procedure selectively labels 5-HT7 receptors. Consistent with a previous report, 3 microM and not 100 nM pindolol was required to occupy fully 5-HT1A and 5-HT1B receptors. Remaining [3H]-5-HT binding was saturable (KD, 1.59+/-0.21 nM; Bmax, 53.8+/-3.1 fmol x mg protein(-1)). Displacement of [3H]-5-HT with metergoline and 5-CT revealed shallow Hill slopes (<0.5) but seven other compounds had slopes >0.8 and pKi values and the rank order of affinity were significantly correlated (r = 0.81 and 0.93, respectively) with published [3H]-5-HT binding to rat recombinant 5-HT7 receptors. In the presence of pindolol, 5-HT-enhanced accumulation of [32P]-cyclic AMP was unaffected by the 5-HT4 antagonist RS39604 (0.1 microM) or the 5-ht6 antagonist Ro 04-6790 (1 microM) but significantly attenuated by mesulergine (250 nM), ritanserin (450 nM) or methiothepin (200 nM) which have high affinity for the 5-HT7 receptor. Intracerebroventricular pretreatment with the serotonergic neurotoxin 5,7-dihydroxytryptamine, 5,7-DHT, elevated the [3H]-5-HT Bmax 2 fold, indicating that the hypothalamic 5-HT7 receptor is post-synaptic to 5-HT nerve terminals and regulated by synaptic 5-HT levels. These results suggest that, in the presence of 3 microM pindolol, [3H]-5-HT selectively labels hypothalamic binding sites consistent with functional 5-HT7 receptors.

5,7-Dihydroxytryptamine↗
PubMed1998

Developmental changes in neurotensin and its metabolites in the neonatal rat.

Neurotensin-like immunoreactivity (NT-LI) was measured in the di-, tel- and mesencephalon of rats from embryonic day 15 (E15) through birth ( approximately E22) until postnatal day 5 (P5) using radioimmunoassay (RIA) and an N-terminal directed polyclonal antibody. NT-LI and NT metabolite-like immunoreactivities (NT 1-8, NT 1-10, NT 1-11 and NT 1-12-LI) were also similarly determined using high performance liquid chromatography (HPLC) coupled with RIA. NT-LI was low at E15 but increased to peak levels at around E20 or birth in the di- and telencephalon, after which the levels declined. Similar, but lower, changes were observed with NT 1-10-LI but not other metabolites while much lower NT-LI and metabolites were observed in the mesencephalon where no transitory changes occurred. The changes in neonatal rat brain NT and metabolites are discussed with respect to the possible neonatal trophic roles of these peptides.

Animals↗
PubMed1998

Maternal cocaine exposure alters mesolimbic dopaminergic function in rat offspring.

Hooded Lister female rats were treated with either saline or cocaine (20 mg/kg s.c.) from gestational day 10 every other day until weaning (postnatal day 25). In vivo microdialysis has shown that maternal cocaine exposure significantly decreases basal extracellular concentrations of dopamine in the nucleus accumbens of young-adult offspring (4 weeks after cessation of cocaine treatment). Moreover, the increase in extracellular dopamine levels induced by a challenge dose of K+ (intracerebral 60 mM K+ artificial cerebrospinal fluid (aCSF) infusion) or cocaine (15 mg/kg i.p.) was significantly attenuated in rats exposed to cocaine during perinatal life with respect to controls. The alterations in mesolimbic dopamine transmission observed in these experiments might underlie behavioral abnormalities induced in rat offspring by maternal exposure to cocaine at dose levels which do not produce gross malformations and/or overt neurotoxic effects.

Animals↗
PubMed1998

Strychnine effects on ultrasound-elicited behaviours in Lister hooded rats.

Previous studies have demonstrated that Lister hooded rats will exhibit characteristic bursts of locomotion when exposed to a 20-kHz acoustic stimulus; this ultrasound-induced locomotion has been suggested as a potential model for panic attacks. Although ultrasound presentation rarely induces convulsions, the locomotor bursts exhibited resemble pre-convulsant running. The present studies examined the interactions between strychnine treatment and experimenter-presented ultrasounds on behaviour in male Lister hooded rats. Strychnine was selected because it is a potent and effective convulsion-inducing agent which is not known to induce anxiety in humans. Behaviour in a circular arena (75 cm diameter) was observed live, videotaped and traced electronically. In experiments 1 and 2, moderate (60 s) or relatively brief (15 s) exposure to an ultrasound stimulus (20 kHz, 98 dB, SPL) typically resulted in 5- to 10-s bursts of locomotion in saline-treated subjects; strychnine treatment (0.5, 0.7, 1.0 mg/kg, injected i.p., 10 min prior to testing) significantly increased this ultrasound-induced locomotion in a dose-dependent manner. Experiment 3 demonstrated that the strychnine enhancement of the ultrasound response was not different in naive animals when compared to those subjects which had received occasional strychnine and/or ultrasound treatment previously. Experiment 3 also demonstrated that strychnine treatment can cause at least modest running in subjects exposed to a 2 kHz tone (96 dB SPL). In experiment 4, exposure to the 20 kHz, 98 dB ultrasound stimulus for a much longer period, 9 min, resulted in irregular cycles of bursts of locomotion, followed immediately by periods of relative inactivity in saline-treated animals; approximately 10% of these subjects exhibited tonic-clonic convulsions. No convulsions occurred in strychnine-treated subjects during the period 10-20 min post-injection in the absence of ultrasound exposure; in contrast, the frequency of occurrence of convulsions in strychnine-treated subjects (10-20 min post-injection) exposed to the ultrasound stimulus was greater than 50%; these convulsions typically occurred at the end of a locomotor burst. The results of the present studies suggest that there may be a relationship between ultrasound-induced locomotor bursts and convulsant activity.

Acoustic Stimulation↗
PubMed1998

Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems.

Isolation rearing of rats produces a behavioral syndrome indicative of altered dopamine (DA) function in the nucleus accumbens (NAC). The present experiments extend these findings by investigating: (a) interactions between isolation rearing and repeated handling/testing on presynaptic DA function in the NAC using in vivo microdialysis: (b) the dose-response curve for the effects of d-amphetamine, and the responses elicited by high potassium, using in vivo microdialysis, and (c) postsynaptic function in isolates as indexed by DA receptor-linked cAMP production. Experiment 1 showed that both isolation rearing and repeated handling/testing had effects on monoamine function in the NAC. However, while both manipulations enhanced DA release evoked by d-amphetamine, only isolated rats had elevated basal DA levels. Opposite neurochemical changes were observed with respect to the serotonin metabolite 5-HIAA, isolates having lower, and repeatedly handled/tested animals having higher, extracellular levels. Experiment 2 provided evidence for enhanced d-amphetamine-evoked DA release in isolated animals, while potassium-evoked DA release was reduced. Experiment 3 provided evidence that the isolation rearing induced changes in presynaptic DA function were accompanied by postsynaptic changes. Specifically, the inhibitory influence of the D2 receptor on D1 receptor-stimulated cAMP production was attenuated in ventral striatal slices taken from isolates, suggesting a functional downregulation of D2 receptors.

Animals↗
PubMed1998

Extracellular dopamine in the anterior nucleus accumbens is distinctly affected by ventral tegmental area administration of cholecystokinin and apomorphine: data from in vivo voltammetry.

The interaction of cholecystokinin (CCK) and dopamine (DA) in the mesolimbic system was investigated. The study focused on DAergic cells not containing colocalized CCK projecting from the ventral tegmental area (VTA) to the anterior nucleus accumbens (NA). Differential pulse voltammetry in pargyline pretreated and anesthetized rats was used to measure extracellular DA in the anterior NA following microinjection of apomorphine either alone or in combination with CCK-8s into the VTA. In agreement with an earlier study there was a dose-dependent increase in the DA signal in the anterior NA after microinjection of CCK-8s into the VTA. Apomorphine microinjected into the VTA produced a biphasic effect on extracellular DA in the anterior NA with an increase from basal levels of approximately 50% by 1 ng, whereas 10 ng was ineffective and 100 ng apomorphine caused a slight decrease in the DA signal. Apomorphine (1 ng) microinjected together with 1 ng CCK-8s produced an increase in the DA signal to approximately 180% of the baseline value, whereas the combination of 1 ng apomorphine and 100 ng CCK-8s was ineffective. When 100 ng apomorphine were microinjected in combination with either 1 ng or 100 ng CCK-8s, the DA signal in the anterior NA was unchanged. These results suggest that low doses of apomorphine injected into the VTA synergistically influence the effects of CCK-8s on extracellular DA in the anterior NA, whereas higher doses of apomorphine suppress the effect of CCK-8s on DAergic cells projecting to the anterior NA.

Anesthesia↗
PubMed1998

Conditioned release of 5-hydroxytryptamine in vivo in the nucleus accumbens following isolation-rearing in the rat.

This study examined the effect of isolation-rearing in the Lister hooded rat on extracellular 5-hydroxytryptamine in the medial nucleus accumbens following footshock and in relation to a conditioned emotional response. Inescapable mild footshock was associated with an immediate and prolonged increase in extracellular 5-hydroxytryptamine in the medial nucleus accumbens of isolation-reared rats. In group-reared rats (footshock-treated) and control groups (no footshock) there was no significant change in extracellular 5-hydroxytryptamine levels. When exposed to the contextual stimulus 140 min later (testing box without shock) there was an immediate and long-lasting increase in extracellular 5-hydroxytryptamine in the nucleus accumbens of the isolation-reared rats, however, the contextual stimulus did not significantly affect extracellular 5-hydroxytryptamine in the medial nucleus accumbens of group-reared rats. The results show that exposure to footshock and conditioning to context are not normally associated with a change in extracellular 5-hydroxytryptamine in the medial nucleus accumbens, however, in rats exposed to social isolation from weaning, both stimuli increase extracellular 5-hydroxytryptamine. The isolation-induced increase in presynaptic serotonergic function in the medial nucleus accumbens contrasts with previous reports of reduced 5-hydroxytryptamine release in the hippocampus and therefore suggests that isolation-rearing differentially affects the function of serotonergic neurons in the brain. The changes in 5-hydroxytryptamine function in the medial nucleus accumbens may represent physiological adaptations to stress or may occur secondary to changes in the function of another neurotransmitter, possibly dopamine.

Animals↗
PubMed1998

Differential effects of neurokinin-1 receptor activation in subregions of the periaqueductal gray matter on conditional and unconditional fear behaviors in rats.

Central neurokinin-1 (NK-1) receptors are thought to modulate aversion, whereas the periaqueductal gray matter (PAG) is a common pathway for the integration of fear behaviors. The authors determined whether injection of an NK-1 agonist (GR73632) into subregions of the PAG would alter fear-related behaviors. Behavioral inactivity was increased by GR73632 injected into the caudodorsal PAG or the dorsal raphe. Flight behavior induced by stimulation of the dorsal PAG or by a footshock was decreased after injection of GR73632 into the dorsal PAG. Rats that had 6 pairings of a tone with a footshock after injection of GR73632 into the dorsal PAG displayed more freezing behavior than controls at the beginning of the session. However, there was no change in the shock- or the tone-induced freezing because some GR73632-treated rats, but no controls, froze during the baseline period. It is concluded that NK-1 receptors in the dorsal PAG modulate the unconditional but not the mnemonic aspects of fear behaviors.

Acoustic Stimulation↗