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J N Crawley

Publications and source records attributed to J N Crawley.

At least 109 records · Page 6Linked to original sources
PubMed1989

Activation in young rats induced by LY134046, an inhibitor of phenylethanolamine N-methyltransferase.

LY134046, a potent, selective inhibitor of rat brain phenylethanolamine N-methyltransferase, was shown to increase activity in 18- and 19-day-old rats. The effects on day 25 were different, with LY134046 causing a decrease in activity. The effects of yohimbine, a selective antagonist of the alpha-2 adrenergic receptor, were markedly different from LY134046, causing a decrease in activity on day 19. These data suggest that epinephrine synthesis may play an inhibitory role in the regulation of activity in young rats.

Animals↗
PubMed1989

A pretest procedure reliably predicts performance in two animal models of inescapable stress.

Rats exposed to inescapable tailshock fail to learn a shuttle-escape task 24 hours later, an effect referred to as "learned helplessness." However, within most rat strains only 10-50% of the animals tested develop this syndrome. In the present study a significant correlation was found between rats that displayed learned helplessness on the first test and those that displayed learned helplessness on a second test performed either 2 weeks (r = .80, p less than 0.001) or 4 weeks (r = .74, p less than 0.001) later. An analysis of the mean session latency of the shuttlebox task in these two tests suggested a bimodal distribution of animals that failed and learned. A significant correlation was found between individual rats that learned this task on the first test and those which learned this task 2 or 4 weeks later. Similarly, in the "behavioral despair" test, a significant correlation was observed for floating time for individual rats on the first test and on the second test either 2 (r = .72, p less than 0.001) or 4 weeks (r = .63, p less than 0.001) later. However, for the forced-swim test, a unimodal and rather graded response was observed across individual subjects. Thus, performance on the first round predicted performance on the second round in both models. When rats experienced the learned helplessness paradigm on round 1 and the behavioral despair paradigm in round 2, there was no correlation between rats that displayed helplessness following inescapable tailshock and the rats that demonstrated "behavioral despair" on a later test.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Co-existence of galanin and acetylcholine: is galanin involved in memory processes and dementia?

Galanin-like immunoreactivity co-exists with choline acetyltransferase-like immunoreactivity in neurons of the septal-hippocampal and nucleus basalis of Meynert-neocortical pathways. These structures mediate some forms of cognition, and characteristically degenerate in Alzheimer's disease. Biochemical, neurophysiological and behavioral studies indicate that galanin acts as an inhibitory modulator of cholinergic function. In this article, we consider the possibility of a role for galanin in memory processes and dementia.

Acetylcholine↗
PubMed1989

Hyperlocomotion induced by dopamine or cholecystokinin + dopamine in the nucleus accumbens is not modified by chronic lithium treatment.

1. Peptides such as cholecystokinin have been reported to modulate the effects of dopaminergic agonists on locomotion in rats. 2. The present experiments tested the possibility that lithium interacts with dopaminergic function through the same mechanism by which cholecystokinin potentiates dopaminergic function. 3. The results suggest that dietary lithium has no effect on the ability of either dopamine alone, or the combination of dopamine plus cholecystokinin, microinjected directly into the nucleus accumbens, to stimulate hyperlocomotion.

Animals↗
PubMed1988

Attenuation of dark-induced hyperlocomotion by a cholecystokinin antagonist in the nucleus accumbens.

A dark-induced hyperlocomotion paradigm was developed to investigate the role of endogenous cholecystokinin in mediating exploratory locomotor activity in the mesolimbic pathway, where cholecystokinin coexists with dopamine. Microinjection of the cholecystokinin receptor antagonist, proglumide, 10-20 micrograms, into the medial posterior nucleus accumbens, significantly inhibited dark-induced hyperlocomotion, while having no effect on locomotion in the light. These data suggest that endogenous cholecystokinin contributes to behaviorally relevant functions of the activated mesolimbic pathway.

Animals↗
PubMed1988

Behavioral evidence for increased acetylcholine receptor sensitivity after nucleus basalis magnocellularis lesions in the rat.

Lesions of the nucleus basalis magnocellularis and the medial septal area have been shown to produce both deficits in memory and decreases in choline acetyltransferase levels. In order to determine whether functional changes in acetylcholine receptor sensitivity also occur, the present experiment examined the ability of acetylcholine, 40 micrograms intraventricularly, to induce motor seizures in nucleus basalis magnocellularis-medial septal area lesioned versus control rats. While choline acetyltransferase activity was only modestly reduced in lesioned rats vs control rats (30%), the seizure scores were considerably higher in lesioned vs. control rats (270%). These results suggest that there is an increased functional response to acetylcholine following bilateral nucleus basalis magnocellularis-medial septal area lesions.

Acetylcholine↗
PubMed1988

(D-Phe12) bombesin and substance P analogues function as central bombesin receptor antagonists.

The potency of synthetic bombesin (BN) analogues with D-Phe12 substitutions and substance P analogues was investigated in the rat CNS. (D-Phe12,Leu14)BN, (D-Phe12)BN and (Tyr4,D-Phe12)BN inhibited binding to rat brain slices with IC50 values of approximately 2 microM. Similarly, spantide inhibited binding to rat brain slices with an IC50 value of 1.5 microM. Spantide inhibited specific (125I-Tyr4)BN binding as a result of decreased rate of association, whereas the rate of dissociation was unaffected. Neither the (D-Phe12)BN analogues nor the substance P analogues inhibited specific binding of 125I-VIP to rat brain slices. Central administration of BN (0.5 micrograms) induced grooming and suppressed feeding and resting. (Tyr4, D-Phe12)BN (5 micrograms) antagonized the behavioral effects of BN. Although spantide (2 micrograms) also antagonized many of the BN effects, it had intrinsic effects and hence the behavioral antagonism was not specific. These data suggest that although both (D-Phe12)BN and substance P analogues may function as central BN receptor antagonists, the (D-Phe12)BN analogues may be functionally the more useful class of antagonists.

Animals↗
PubMed1988

Potency of L-364,718 as an antagonist of the behavioral effects of peripherally administered cholecystokinin.

A new antagonist of the peripheral cholecystokinin receptor, L-364,718, was found to block the reductions in food intake and exploratory activity induced by intraperitoneal administration of cholecystokinin octapeptide sulfate. L-364,718 significantly reversed the cholecystokinin-induced reduction in feeding at doses of 10 micrograms/kg - 10 mg/kg i.p. L-364,718 significantly reversed the cholecystokinin-induced reduction in exploratory activity at doses of 500 ng/kg - 10 mg/kg i.p. The time course of antagonist activity of L-364,718 was immediate to 90 minutes after intraperitoneal administration. L-364,718 had no significant effect on food intake or exploratory activity when administered alone, over the dose range of 100 ng/kg-10 mg/kg i.p. This compound appears to be at least one hundred times more potent than proglumide or benzotript as an antagonist of the behavioral effects of peripherally administered cholecystokinin.

Animals↗
PubMed1988

Characterization of stress-induced alterations in [3H] Ro5-4864 binding to peripheral benzodiazepine receptors in rat heart and kidney.

Inescapable tailshock has been shown to elicit a tissue specific decrease in the density of peripheral benzodiazepine receptors (PBR). We have now explored possible mechanisms that may be responsible for this phenomenon. An 80 minute session of inescapable tailshock produced a reduction in the binding of [3H] Ro5-4864 to renal membranes at 0, 1 and 2 hr after stress, with values returning to control (naive) levels within 24 hr. In cardiac membranes, statistically significant reductions were observed only at 2 and 4 hr after stress. The role of the pituitary-adrenal axis and the sympathetic nervous system in this phenomenon was assessed by subjecting adrenalectomized, hypophysectomized, 6-OHDA-treated or control (sham-operated or saline-treated) rats to inescapable shock. Neither adrenalectomy, hypophysectomy, nor 6-OHDA pretreatment altered the stress-induced reduction in renal PBR. However, the stress-induced decrease in renal PBR was blocked by pretreatment with clonazepam (1 mg/kg), a potent anxiolytic with low affinity for PBR.

Adrenalectomy↗
PubMed1988

Anatomical analysis of frontal cortex sites at which carbachol induces motor seizures in the rat.

High amplitude spiking representative of seizures, accompanied by an unusual motor behavior pattern of rearing and forelimbic clonus resembling "boxing," was elicited by microinjection of the cholinergic agonist, carbachol, 4 micrograms, into the medial prefrontal cortex of the rat. A rating scale devised to score the behavior revealed a motor pattern elicited by carbachol from the medial anterior cortex which was similar to that described by Racine for electrical stimulation of the amygdala. Topographical analysis of the areas surrounding the medial anterior cortex region revealed that the motor manifestations of seizures were elicited over a wide region of the anterior cortex, with scores significantly lower at carbachol microinjection sites greater than 1 mm rostral, 2 and 3 mm caudal, and 2 mm lateral to the standard medial prefrontal cortex site. Unilateral microinjection of carbachol yielded motor seizures primarily from the contralateral forepaw, suggesting involvement of a crossed pathway. Retrograde tracing with fast blue dye, combined with immunostaining for choline acetyltransferase and NADPH-diaphorase, found that the cholinergic neurons innervating the standard microinjection site were the dorsolateral tegmental cells, as previously reported, which have been shown to also contain substance P and corticotropin releasing factor. In addition, cholinergic neurons of the nucleus basalis of Meynert region were found to innervate the standard microinjection site. These findings implicate cholinergic innervation of the rostral cortex in classical limbic seizures.

Animals↗
PubMed1988

Substance P antagonists block carbachol-induced "boxing" behavior at a site of coexistence in the rat prefrontal cortex.

A cholinergic projection from the dorsolateral tegmentum to the medial anterior cortex has previously been shown to contain substance P and corticotropin releasing factor. Behavioral analysis of acetylcholine, substance P and corticotropin releasing factor microinjected into the medial anterior cortex revealed a seizure-related "boxing" behavior elicited by carbachol, which was potentiated by coinjection with substance P and antagonized by coinjection with corticotropin releasing factor. We now report that two antagonists of substance P receptors, [D-Pro2, D-Phe7, D-Trp9]-substance P and [D-Pro2, D-Trp7,9]-substance P, attenuate "boxing" behavior when coinjected with carbachol. Neither antagonist produced observable behavioral effects when microinjected alone. An analog of substance P, [pGlu,5, MePhe,8 Sar9]-substance P (5-11) potentiated carbachol-induced "boxing" at doses similar to naturally-occurring substance P. Monoclonal and polyclonal antisera against substance P were not effective antagonists of carbachol-induced "boxing." The ability of substance P antagonists to block carbachol-induced "boxing" has two major implications: (1) endogenous substance P may be modulating endogenous acetylcholine in the tegmental-cortical pathway; and (2) substance P antagonists may provide a new avenue for the development of antiepileptic drugs.

Amino Acid Sequence↗
PubMed1988

Ventral tegmental oxytocin induces grooming.

Bilateral microinjection of oxytocin (OXY) into the ventral tegmental area (VTA) of rat brain produced a significant increase in grooming behaviors at doses from 100 pg to 400 ng. Sites in the caudal region of the VTA were sensitive to lower doses of OXY than sites in the rostral region of the VTA. The time course of action of OXY in the grooming paradigm indicated onset beginning immediately after injection, and termination at 60-75 minutes after injection. Comparison of OXY-induced grooming in male, female, and ovariectomized, estrogen-treated female rats showed no differences in potency for OXY among these groups, suggesting that the grooming effects of OXY are not regulated by sex steroids. Analysis of locomotor activity in rats microinjected with OXY 200 ng bilaterally into the caudal VTA revealed that OXY had no effect on ambulatory locomotion, suggesting that this peptide may activate neurons within the VTA which mediate grooming but not locomotion. The OXY receptor antagonist, [Pen1, pMePhe2, Thr4, Orn8]-OT, blocked OXY-induced grooming when both were simultaneously microinjected into the VTA. The dopamine D-2 receptor antagonist, haloperidol, and the D-1 receptor antagonist, SCH 23390, when microinjected into the VTA five minutes before microinjection of OXY into the VTA, did not block OXY-induced grooming, suggesting that OXY is not working through a dopamine autoreceptor on the VTA neurons. Systemic pretreatment with haloperidol and SCH 23390 effectively blocked grooming induced by OXY in the VTA, suggesting that OXY is directly stimulating OXY receptors on VTA neurons to release dopamine at postsynaptic sites regulating grooming behaviors.

Animals↗
PubMed1988

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

Galanin coexists with acetylcholine in medial septal neurons projecting to the ventral hippocampus, a projection thought to modulate memory functions. Neurochemical lesions of the nucleus basalis-medial septal area in rats impaired choice accuracy on a delayed alternation t-maze task. Acetylcholine (7.5 or 10 micrograms intraventricularly or 1 micrograms micro-injected into the ventral hippocampus) significantly improved performance in the lesioned rats. Atropine (5 mg/kg intraperitoneally or 10 micrograms intraventricularly), but not mecamylamine (3 mg/kg intraperitoneally or 20 micrograms intraventricularly), blocked this action of acetylcholine, suggesting involvement of a muscarinic receptor. Galanin (100-500 ng intraventricularly or 200 ng into the ventral hippocampus) attenuated the ability of acetylcholine to reverse the deficit in working memory in the lesioned rats. The antagonistic interaction between galanin and acetylcholine suggests that endogenous galanin may inhibit cholinergic function in memory processes, particularly in pathologies such as Alzheimer disease that involve degeneration of basal forebrain neurons.

Acetylcholine↗
PubMed1988

The effects of anxiolytics and other agents on rat grooming behavior.

BN and other peptides increase grooming activity in rodents. This increase in grooming activity caused by BN can be reversed by numerous agents. The most direct of these are BN receptor antagonists such as spantide and [D-Phe-12]BN. These agents reverse the increase in grooming activity caused by BN and inhibit binding to central BN receptors. The increase in grooming activity caused by BN may be mediated by other neurotransmitters, such as dopamine. In this regard the increase in grooming activity caused by BN is reversed by fluphenazine and haloperidol. These agents do not affect binding to central BN receptors. Similarly, the increase in grooming caused by BN is absent if dopamine-containing neurons are lesioned with 6-OHDA. These lesions cause a significant reduction in central BN receptors, especially in the central amygdaloid nucleus. Thus some of the BN receptors may be present on dopamine-containing neurons. The increase in grooming activity caused by BN was also reversed by diazepam and chlordiazepoxide. Neither of these agents affected binding to central BN receptors, and similarly, BN did not affect binding to central benzodiazepine receptors. Thus anxiolytics may act at a site anatomically downstream from the BN receptor and reduce the apparent stress caused by central injection of BN.

Animals↗
PubMed1988

Effects of Ro15-4513 and other benzodiazepine receptor inverse agonists on alcohol-induced intoxication in the rat.

The ability of the imidazobenzodiazepine Ro15-4513 to antagonize the behavioral intoxication produced by ethanol and related short-chain alcohols was examined in the rat. Ro15-4513 dose dependently (0.5-10 mg/kg i.p.: IC50, 1.5 mg/kg) inhibited the intoxication induced by ethanol (2 g/kg), as well as t-amyl alcohol (0.36 g/kg) and methanol (4.66 g/kg). The effects of Ro15-4513 in blocking ethanol-induced intoxication were blocked by the benzodiazepine receptor antagonists Ro15-1788 and CGS-8216. However, Ro15-4513 was ineffective in antagonizing the intoxication observed after higher doses of ethanol (4 g/kg). In contrast, ethanol-induced intoxication was not antagonized by the benzodiazepine receptor antagonists Ro15-1788 (10 mg/kg) or CGS-8216 (20 mg/kg), nor by the inverse agonists FG-7142 (10-30 mg/kg) or beta CCE (10 mg/kg). When administered after ethanol, Ro15-4513 also reversed ethanol-induced intoxication in a dose-dependent manner (2.5-10 mg/kg i.p.: IC50, 5 mg/kg), an effect which was also blocked by Ro15-1788 and CGS-8216. However, neither beta CCE (10 mg/kg) or FG-7142 (less than or equal to 30 mg/kg) alone reversed ethanol-induced intoxication. Moreover, beta CCE (10 mg/kg), when administered just before Ro15-4513, completely antagonized the actions of Ro15-4513 in reversing ethanol-induced intoxication. These data suggest that the ability of Ro15-4513 to antagonize, and to reverse, ethanol-induced intoxication is mediated via central benzodiazepine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholic Intoxication↗
PubMed1987

Oxytocin and cholecystokinin induce grooming behavior in the ventral tegmentum of the rat.

Oxytocin (OXY) and cholecystokinin (CCK) coexist in neurons of the supraoptic nucleus and the paraventricular nucleus of the hypothalamus of the rat (Cell Tissue Res., 221 (1981) 227-231). Behavioral analysis of one possible terminal field of the OXY-CCK coexistence, the caudal region of the mesencephalic ventral tegmentum, was undertaken to investigate the functional significance of this coexistence. Both OXY and CCK were found to induce grooming behaviors when microinjected into the ventral tegmental area (VTA) of awake rats. Combinations of one low and one higher dose of OXY and CCK yielded grooming scores which were not significantly different from grooming scores induced by each peptide alone. In this case of putative coexistence of two peptides without a 'classical' neurotransmitter, each peptide appears to have a behavioral function, and the interaction between the two peptides may be competitive.

Animals↗
PubMed1987

Neuropeptide modulation of apomorphine-induced stereotyped behavior.

The nucleus accumbens contains many neuropeptides whose functions are presently unknown. The purpose of this study was to determine the extent to which these neuropeptides act in conjunction with the mesolimbic dopamine system. Microinjections of cholecystokinin, neurotensin, met-enkephalin, somatostatin, bombesin, as well as glutamate and muscimol, were made into the medial nucleus accumbens after systemic injection of apomorphine. Cholecystokinin and neurotensin, in nanogram doses, potentiated apomorphine-induced stereotypy. Met-enkephalin reduced, while somatostatin and bombesin were without effect on, apomorphine-induced stereotypy. In addition, both glutamate and muscimol potentiated this effect. These results suggest that several neuropeptides and amino acids act in the nucleus accumbens to modulate apomorphine-induced stereotyped behaviors.

Animals↗