Effects of intraventricular administration of cholecystokinin octapeptide sulfate ester and unsulfated cholecystokinin octapeptide on active avoidance and conditioned feeding behaviour of rats

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and unsulfated cholecystokinin (CCK-8-NS) were studied following intraventricular administration on active avoidance and conditioned feeding behaviour of rats. In the CCK-8-NS and CCK-8-SE treated animals the acquisition of active avoidance and conditioned feeding behaviour were considerably impaired compared to the control; furthermore, these peptides caused a facilitated extinction of active avoidance and conditioned feeding behaviour. The data suggest that cholecystokinin octapeptide is capable of modifying the fear and hunger motivated behaviours of rats.     

Effects of cholecystokinin octapeptide sulphate ester and unsulphated cholecystokinin octapeptide on active avoidance behaviour in rats

The effects of peripherally administered cholecystokinin octapeptide sulphate ester and its unsulphated form on the active avoidance behaviour of rats were studied. The acquisition of avoidance behaviour was impaired, while extinction was facilitated, following cholecystokinin octapeptide sulphate ester or unsulphated cholecystokinin octapeptide treatment. These peptides had no action on open-field activity. It is concluded that peripherally administered cholecystokinin octapeptide influences acquisition and extinction of active avoidance behaviour and this effect is unrelated to general motor activity of the animals.     

Drug-induced conditioned place preference and aversion in mice

This protocol describes the equipment and methods used to establish conditioned place preference (CPP) or aversion (CPA). Place conditioning is a form of Pavlovian conditioning routinely used to measure the rewarding or aversive motivational effects of objects or experiences (e.g., abused drugs). Here, we present a place conditioning procedure that has been used extensively to study the motivational effects of ethanol and other abused drugs in mice. This protocol involves three phases: (i) habituation (or a pretest), (ii) conditioning of an association between the drug and a tactile or visual stimulus and (iii) a test that offers a choice between the drug-associated cue and a neutral cue. If the drug has motivational significance, mice will spend significantly more time (CPP) or less time (CPA) in proximity to the drug-associated cue. Potential problems in the design and interpretation of place conditioning studies are discussed. A typical experiment lasts 2 weeks.     

Effects of propranolol on acquisition and retrieval of morphine- induced conditioned place preference memories in ICR mice

To interfere with the drug-cue memory processes of addicts such as reconsolidation by the administration of the β-adrenergic receptor (β-AR) of norepinephrine (NE) antagonist propranolol (PRO) has become a potential therapy in the future to decrease or inhibit relapse. However, the relationship between PRO and the acquisition or retrieval of morphine-cue memory is not clear. This study examined the effects of PRO on the acquisition and retrieval of memories in morphine-induced conditioned place preference (CPP) mice model. We found that during memory acquisition period, PRO had no effects on the expression and extinction of morphine-CPP, which suggests that the β-AR was irrelevant to the CPP memory acquisition. However, during memory retrieval period, although PRO did not affect the expression of CPP, but it delayed the occurrence of CPP extinction, which indicates that PRO has an inhibit effect on CPP memory extinction, and β-AR plays an important role in modulating the extinction of morphine-CPP. Our study further improved the relationship between drug addiction and β-AR, and proposed a new theory to help developing potential therapy to cure addiction and other neuropsychiatric disorders.     

Behavioral effect of cholecystokinin octapeptide in vagotomized rats

Cholecystokinin octapeptide (CCK-8) was administered intracerebroventricularly (icv) or subcutaneously (sc) into subdiaphragmatically vagotomized and sham-operated rats, and the behavioral effects were quantified by an open-field test. Intracerebroventricularly injection of CCK-8 decreased locomotion and rearing to the same extent in both vagotomized and sham-operated rats, while sc injection produced behavioral changes only in sham-operated rats but not in vagotomized ones. The results indicate that CCK-8 affects both central and peripheral receptors, and the vagal nerve may be the major pathway causing behavioral effects from the visceral organs to the brain.     

Extinction of conditioned opiate withdrawal in rats in a two-chambered place conditioning apparatus

Conditioned opiate withdrawal contributes to relapse in addicts and can be studied in rats by using the opiate withdrawal-induced conditioned place aversion (OW-CPA) paradigm. Attenuation of conditioned withdrawal through extinction may be beneficial in the treatment of addiction. Here we describe a protocol for studying OW-CPA extinction using a two-chambered place conditioning apparatus. Rats are made dependent on morphine through subcutaneous implantation of morphine pellets and then are trained to acquire OW-CPA through pairings of one chamber with naloxone-precipitated withdrawal and the other chamber with saline. Extinction training consists of re-exposures to both chambers in the absence of precipitated withdrawal. Rats tested after the completion of training show a decline in avoidance of the formerly naloxone-paired chamber with increasing numbers of extinction training sessions. The protocol takes a minimum of 7 d; the exact duration varies with the amount of extinction training, which is determined by the goals of the experiment.     

Preventive effect of cholecystokinin octapeptide on experimental amnesia in rats

The effect of intracerebroventricular (ICV) administration of cholecystokinin octapeptide (CCK-8) on electroconvulsive shock (ECS)-induced amnesia in passive avoidance response was studied in rats. In normal rats, CCK-8 in doses from 1 ng to 1 microgram had no effect on the response when injected before the training trials, immediately after foot shock or before the first retention test. However, proglumide, a CCK-8 receptor blocker, induced marked amnesia when injected in doses from 0.1 to 10 micrograms before the training trials and in doses of 1 and 10 micrograms before the first retention test, though not subsequent to foot shock. ECS given immediately after the foot shock caused amnesia in the 24 hr and 48 hr retention tests, which could have been prevented by CCK-8 injected in doses of 10 ng to 1 microgram prior to the training trials, of 10 ng to 1 microgram following ECS and of 0.1 and 1 microgram before the first retention test. In addition, the effects of CCK-8 and proglumide became pronounced following chronic ICV infusion, using an osmotic minipump, for 7 days at a dose of 1 ng/day and 10 ng/day, respectively. The amnesia induced by proglumide was not affected by arginine vasopressin (AVP), while AVP in doses of 10 ng and 100 ng given 30 min before the training trials prevented ECS-induced amnesia. The antiamnesic effect of AVP was abolished by simultaneous administration of proglumide. On the other hand, AVP-antiserum produced marked amnesia which could be antagonized by CCK-8. However, the antiamnesic effect of CCK-8 was not suppressed by AVP-antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of acute corticosterone on lithium chloride-induced conditioned place aversion and locomotor activity in rats

Acute administration of corticosterone (CORT) facilitates learning in a number of associative paradigms including lithium chloride (LiCl)-induced conditioned taste aversion learning. The present study examined the effects of acute CORT on LiCl-induced conditioned place aversions in male rats. Automated open-fields were partitioned into two chambers distinct in tactile and visual cues. Animals received either LiCl (64 mg/kg, 0.15 M) or saline (NaCl, 0.15 M) followed 10 min later by either CORT (5 mg/kg) or beta-cyclodextrin vehicle (45%) prior to placement in one of the chambers. Control rats received NaCl-Vehicle paired with both chambers. Three experimental groups received either NaCl-CORT, LiCl-Vehicle or LiCl-CORT paired with the preferred chamber and NaCl-Vehicle (control) paired with the non-preferred chamber. During extinction trials, animals were allowed to choose between the two chambers. Locomotor activity and its distribution within the chambers were assessed during both conditioning and extinction trials. CORT administration produced significant increases in a variety of measures of locomotor activity during conditioning trials. During extinction trials both LiCl groups displayed a conditioned place aversion while the NaCl-CORT group did not. In addition, significant increases in vertical activity were recorded in both LiCl groups in the LiCl-paired chamber. Moreover, CORT administration had no effect on LiCl-induced conditioned place aversion as time spent in the LiCl-paired chamber did not significantly differ between LiCl-Vehicle and LiCl-CORT groups. Significant increases in a number of measures of horizontal activity were also observed in both CORT groups. The present study shows that acute CORT administration does not significantly influence LiCl-induced conditioned place aversions and suggests that the facilitatory effects of acute CORT administration on learning are highly context-dependent.     

GABA neurons of the VTA drive conditioned place aversion

Salient but aversive stimuli inhibit the majority of dopamine (DA) neurons in the ventral tegmental area (VTA) and cause conditioned place aversion (CPA). The cellular mechanism underlying DA neuron inhibition has not been investigated and the causal link to behavior remains elusive. Here, we show that GABA neurons of the VTA inhibit DA neurons through neurotransmission at GABA(A) receptors. We also observe that GABA neurons increase their firing in response to a footshock and provide evidence that driving GABA neurons with optogenetic effectors is sufficient to affect behavior. Taken together, our data demonstrate that synaptic inhibition of DA neurons drives place aversion.     

Modulation of passive avoidance behaviour of rats by intracerebroventricular administration of cholecystokinin octapeptide sulfate ester and nonsulfated cholecystokinin octapeptide

The effects of intracerebroventricular administration of different doses of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated cholecystokinin octapeptide (CCK-8-NS) were tested on the latency of passive avoidance behaviour in rats. Treatments were carried out prior to learning trial, immediately after electroshock and prior to testing 24 h retention. Both CCK-8-NS and CCK-8-SE enhanced the latency of passive avoidance after all forms of treatment while showing different dose-response patterns depending on time of administration. These data indicate that CCK-8-SE and CCK-8-NS might play a role in the regulation of memory consolidation and retrieval.     

Stimulus specificity in the acquisition and extinction of conditioned taste aversion

An experiment evaluated whether the acquisition and extinction of conditioned taste aversion in the rat is stimulus-specific by testing the degree of response transfer between sweet and salty tastes. Animals in the paired-same and paired-different groups received a presentation of a gustatory CS and a cyclophosphamide injection US. Nonconditioned control groups received unpaired CS /US presentations or the CS followed by a vehicle injection. Taste avoidance was evaluated in three nonreinforced test sessions. In the paired-same, unpaired and vehicle groups, all test sessions were conducted with the same flavor as originally used in training, whereas the paired-different group was tested with a novel flavor on the first and second sessions and with the originally trained flavor in last session. Stimulus specific acquisition was apparent in the first test session, when the animals in the group paired-same exhibited lower fluid intake than the other three groups. Evidence of specificity of extinction was apparent in the last test session, when animals in the group paired-different exhibited lower fluid intake than the other three groups. These results provide further evidence of stimulus specificity in acquisition and extinction of conditioned taste aversion, supporting the associative interpretation of these phenomena.     

心得安对ICR小鼠吗啡诱导的条件化位置偏爱记忆获得和提取的影响

利用心得安阻断β-肾上腺素受体(β-受体),从而干扰药物成瘾患者对药物环境线索记忆的某些环节(如再巩固等),进而降低或抑制其对成瘾药物的渴求,已成为未来治疗复吸的潜在途径.但目前,心得安对吗啡相关环境线索记忆的获得及提取的影响尚不清楚.因此,该实验检测了心得安对小鼠吗啡诱导的条件化位置偏爱(conditioned place preference,CPP)环境线索记忆的获得和提取的影响.该研究首次发现在吗啡CPP记忆的获得期,心得安不影响CPP的表达和消退,提示β-受体不参与吗啡诱导CPP学习记忆的获得;而在吗啡CPP记忆的提取期,心得安可延缓CPP的消退,提示β-受体与吗啡诱导CPP学习记忆的提取相关.该结果表明,药物成瘾过程与β-受体相关,为成瘾等精神疾病的治疗提供了新的理论依据.     

Parabrachial unit activities after the acquisition of conditioned taste aversion to a non-preferred HCl solution in rats

Abstract In a behavioral experiment, rats reliably acquired a taste aversion to non-preferred 0.01 M HCl that had been previously paired with intraperitoneal injection of 0.15 M LiCl. These rats showed aversions to other acidic solutions such as malic acid and tartaric acid. In a neurophysiological experiment, the neuronal activities of the parabrachial nucleus (PBN) were recorded after the acquisition of conditioned taste aversion (CTA) to 0.01 M HCl in urethane-anesthetized rats. Neuronal responses to the conditioned stimulus (CS) did not change on the whole but decreased in the dorsal region to the brachium conjunctivum. The proportion of HCl-best to NaCl-best units was lower in the CTA group than in controls. The spontaneous firing rate was lower in the CTA group than in controls. Correlation coefficients between the HCl CS and normally preferred tastes (sucrose and NaCl) were more negative and those between HCl and quinine were more positive in the CTA group than in the controls. These results may be explained by the notion that gustatory responses of PBN neurons are concerned with alterations in taste hedonics after the acquisition of conditioned taste aversions.     

Effects of cholecystokinin octapeptide on the pancreatic exocrine secretion in the pig

In conscious pigs, intravenous infusion of serial doses of cholecystokinin octapeptide (CCK8; 2.9-232.3 pmol.kg-1.min-1) upon a background of secretin resulted in a linear increase of plasma CCK-like immunoreactivity (CCK-LI) concentration and evoked a dose-related increase of pancreatic volume and bicarbonate and protein outputs. The threshold plasma CCK-LI concentration for significant pancreatic response was 103.8 +/- 10.2 pM using a CCK8 dose of 8.8 pmol.kg-1.min-1. The maximum pancreatic response was observed for a plasma CCK-LI level of 498.0 +/- 15.3 pM using 77.2 pmol CCK8.kg-1.min-1. In anesthetized pigs, the threshold plasma CCK-LI concentration for pancreatic response was 1500 pM (actual CCK8 dose of 60.3 pmol.kg-1.min-1). The physiological relevance of this finding was assessed by comparing the food-induced increase of pancreatic secretion with that of plasma CCK-LI. Food ingestion was followed by a sharp pancreatic response and by a progressive increase of plasma CCK-LI to a peak increment of about 15 pM. Gel chromatography of portal and peripheral plasma from fed animals revealed three major peaks in the volumes of CCK33/39 and CCK8, and in a volume intermediate between CCK33/39 and CCK8. An additional minor component eluted ahead of CCK33/39. CCK8, which is one of the CCK components released after food intake, appears to be a fairly weak pancreatic stimulant in pigs.