Mesencephalic lesions in female rats resulting in normophagia and reduced body weight.

The effects of bilateral mescencephalic lesions in the area of the ventral noradrenergic bundle (VNA) were studied in immature and mature female rats. The food intake consumption of the immature lesioned rats did not differ from sham operated controls whether fed a chow or high fat diet. However, after the surgery the body weights of the two groups began to diverge with the immature lesioned rats obtaining a significantly lower body weight. By the end of the study the immature lesioned rats were also significantly shorter than the controls. Both groups showed normal body composition throughout the measurement period. Upon refeeding after a one day fast the immature female rats defended their lower than normal pre-fast body weight. These data are in good agreement with our earlier findings using immature male rats. The mature lesioned animals also showed normal food consumption when fed a chow type diet. However the lesioned animals did show a brief hyperphagia when placed on a high fat diet. Unlike the immature lesioned rats the body weight of these lesioned animals did not differ from their sham operated controls. It is suggested that lesions in the area of the VNA may result in hyperphagia or, in no effects on food intake or body weight as reported by others or normophagia with reduced body weight. Exact lesion placement may be responsible for these divergent findings.     

Reinnervation of the nucleus accumbens and frontal cortex of the rat by dopaminergic grafts and effects on hoarding behavior

Embryonic dopaminergic neurons were implanted in the form of a cellular suspension in the nucleus accumbens previously deprived of its dopaminergic innervation by a local injection of 6-hydroxydopamine. The graft provided a dopaminergic reinnervation to the nucleus accumbens, the anteromedial striatum, the anteromedial frontal cortex and also, in some cases, of the septum. The pattern of reinnervation was specific for each structure and similar to the innervation provided by mesocorticolimbic dopaminergic neurons to these same structures in the normal animal. The graft restored the locomotor stimulatory action of amphetamine which was abolished in the lesioned controls. Hoarding behavior, which was disrupted following the lesion, was not reinstated by the graft alone. However, if the grafted neurons were stimulated by a small dose (0.2 mg/kg, i.p.) of (+)-amphetamine, hoarding reappeared in the grafted animals, while the same dose of amphetamine had no effect in the lesioned controls.     

Effects of monaural and binaural sound deprivation on cell development in the anteroventral cochlear nucleus of rats

The sizes of large spherical and fusiform cells of the anteroventral cochlear nucleus were studied in rats reared after unilateral middle ear ossicle removal on postnatal days 10 or 16, or after bilateral removal on postnatal day 16. In animals deprived monaurally from 10 days after birth, large spherical cell areas of the deprived side were reduced by 21% compared to the nondeprived side; the deprived cells were 17% smaller than cells of control animals. Large spherical cells contralateral to the deprived ear were slightly larger than those of controls. Large spherical cells monaurally deprived from the 16th day showed effects similar to those deprived from the onset of hearing, although cell reduction on the deprived side was only 10% relative to controls. In contrast to the consequences of monaural sound deprivation, binaural deprivation from the 16th day resulted in no reduction in size of large spherical cells. Fusiform cells of animals in monaurally and binaurally deprived groups were not significantly smaller than the fusiform cells of controls. Ear histologies confirmed that each cochlea and spiral ganglion was normal in experimental and control animals. Because large spherical cells receive unilateral input directly from the acoustic nerve and are known to project bilaterally to the medial superior olive, the bilateral differences observed in large spherical cell area following rearing under monaural deprivation conditions may reflect a form of imbalanced binaural interactions between axon terminals of spherical cells.     

Nicotine infusion into rat ventromedial nuclei and effects on monoaminergic system

Nicotine increases satiety and reduces food intake (FI). We hypothesize that nicotine influences FI via alteration of serotonin (5HT) and dopamine (DA) concentration in ventromedial nucleus (VMN) and lateral hypothalamic area (LHA). Microdialysis cannulas were implanted into ipsilateral VMN and contralateral LHA. Nicotine or vehicle was infused for 60 min into VMN of overnight food-deprived rats, followed by ad lib food for 40 min. Hypothalamic changes in 5HT and DA concentrations were measured every 20 min. Intra-VMN nicotine induced a long-lasting increase in 5HT concentration and an increase in DA for a short duration in the VMN, associated with an increase in 5HT in the LHA. Our data suggest that the nicotine-induced hypophagia correlates with VMN and LHA monoaminergic changes.     

The effect of naloxone on operant behavior for food reinforcers in DBA/2 mice

Mice are powerful models to investigate the genetic basis of food reward because many spontaneous obesity mutants exist and the murine genome is accessible to selectively targeted manipulations. Experiments in rats have shown that opioid receptor blockade reduces operant responding to food reinforcers. The present study investigated whether DBA/2J mice would display similar behavior in response to an opioid antagonist. Twelve male DBA/2J mice were trained to lever press for food reinforcers and subsequently randomized in a within subjects design for no injection, saline injection, or 10 mg/kg naloxone injection intraperitoneal (i.p.) 20 min before each daily trial under ad lib or food-deprived conditions. A significant main effect of injection occurred to reduce lever pressing by the mice. However, a greater pharmacological effect of naloxone occurred compared with saline on the operant responding only under the food-deprived conditions. Interestingly, the percentage of dispensed food pellets actually consumed was significantly reduced after naloxone injection compared with saline injection for either chow-based or sucrose pellets under ad lib or deprived feeding conditions. These data suggest that opioids specifically influence consumatory behavior in mice, but our findings on instrumental behavior were confounded by an independent inhibitory effect of an i.p. saline injection.     

Lesions of mediodorsal thalamus and anterior thalamic nuclei produce dissociable effects on instrumental conditioning in rats

Two experiments examined the effects of bilateral excitotoxic lesions of either the mediodorsal (MD) or anterior (ANT) thalamic nuclei on instrumental acquisition and performance, sensitivity to changes in the value of the instrumental outcome, and sensitivity to changes in the instrumental contingency. Rats were food deprived and trained to press two levers, each earning a unique food outcome (pellets or sucrose). All rats acquired the instrumental response although ANT lesions appear slightly to increase and MD lesions slightly to suppress instrumental performance. After training, specific satiety-induced devaluation of one of the two instrumental outcomes produced a selective reduction in responding on the lever that in training had earned the now devalued outcome but only in the SHAM and ANT groups. In contrast, MD animals failed to show evidence of a selective devaluation effect when tested in extinction. Additionally, SHAM and ANT animals selectively decreased responding when one action-outcome contingency was degraded, whereas MD animals reduced responding nonselectively on the two levers. Subsequent tests established that an inability to discriminate between either the two actions or the two outcomes cannot account for the lack of selective responding observed in the MD animals. Together these data suggest that MD lesions produce a profound deficit in the ability of rats to utilize specific action-outcome associations and appear to render rats relatively insensitive to the causal consequences of their instrumental actions. In contrast, far from producing a deficit, ANT lesioned rats were as sensitive to the effects of these behavioural manipulations as the sham lesioned controls.     

An examination of the effects of bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus on responding to sucrose reward

The effects of bilateral excitotoxic lesions of the pedunculopontine tegmental nucleus (PPTg) on sucrose intake were examined in three experiments. First, in tests of conditioned place preference using 20% sucrose as the reinforcer, it was shown that lesioned rats, regardless of whether they were food deprived or non-deprived, formed normal place preferences and showed normal amounts of locomotion. However, consumption of 20% sucrose in the pairing trials was increased in the deprived PPTg lesioned rats compared to their matched controls. A second experiment showed that sucrose consumption in the home cage was increased in both deprived and non-deprived PPTg lesioned rats, but only when the concentration of sucrose was greater than 12%: below this there were no differences in intake between the lesioned and control rats. In a third home cage experiment, it was again shown that non-deprived PPTg lesioned rats increased their consumption of 20% sucrose compared to controls. PPTg lesioned rats concomitantly reduced their intake of lab chow such that overall energy intake remained the same as that of control rats. These data are taken to suggest (i) that bilateral excitotoxic lesions of the PPTg increase consumption of sucrose selectively in conditions of high motivational excitement; (ii) that the perception of the rewarding value of 20% sucrose, as judged by place preference, is not affected by these lesions; and (iii) that PPTg lesioned rats are able to adjust their energy intake to accommodate increased sucrose loads. These data are consistent with the hypothesis that bilateral excitotoxic lesions of the PPTg do not affect energy balance regulation or judgment of the hedonic value of sucrose, but that they do affect the control of responding in the face of high levels of motivational excitement.     

Effect of early postnatal social and nutritional deprivation and simultaneous treatment with pyridostigmine on synaptogenesis in the hippocampus of the rat. Electron microscopy, morphometric and stereologic studies

During the first two weeks of life newborn male Wistar rats were subjected to social and nutritional deprivation. One group of the deprived animals was treated by daily injections of pyridostigmine (1 microgram/0.05 ml saline from Day 1 to Day 4, 5 micrograms/0.05 ml saline from Day 5 to Day 14). At the age of 14 days or 6 months, 5 deprived, 5 deprived and pyridostigmine treated animals and 5 controls were sacrificed by perfusion. The stratum radiatum of the hippocampal CA1-region was investigated for quantitative ultrastructural changes using electron microscopic, morphometric and stereologic methods. The following results were obtained: The number of synapses per unit area or per unit volume brain tissue (hippocampus) was found to be reduced by about 10% in 14 days old deprived as well as in deprived and pyridostigmine treated rats in comparison to the controls. At the age of 6 months both groups of the experimental animals showed an increase in the density of synapses by about 20% when compared to the controls. The proportion of axo-spinodendritic synapses in the total number of synapses (axo-dendritic and axo-spinodendritic synapses) was decreased on Day 14 and was increased at the age of 6 months in the neonatally deprived rats. Following additional pyridostigmine treatment, both in the juvenile and in the adult rats the ratio of axo-spinodendritic to axo-dendritic synapses was approximated to that of the controls. The calculation of the volume of all presynaptic terminals or all postsynaptic spines per unit volume brain tissue (volume density) revealed a decrease by about 6% (terminals) or 5% (spines) on Day 14 after deprivation and an increase by about 8% (terminals) or 14% (spines) following simultaneous pyridostigmine administration. At the age of 6 months the presynaptic terminals in early postnatally deprived rats showed a higher volume density by about 14%. In the deprived and pyridostigmine treated animals volume density enhancements were obtained for the terminals (by about 7%) and for the spines (by about 25%). The volume and surface of an individual presynaptic terminal were unchanged in 14 days old as well as in 6 months old deprived rats in comparison to the controls. Deprivation and simultaneous pyridostigmine treatment led to an increase in the volume (by about 25%) and the surface (by about 12%) of the terminals on Day 14. However, at the age of 6 months the volume and surface were reduced by about 14% or 12% when compared to the controls.(ABSTRACT TRUNCATED AT 400 WORDS)     

Scopolamine-induced convulsions in fasted mice after food intake: the effect of duration of food deprivation

It has been shown that mice and rats treated with antimuscarinic drugs, scopolamine or atropine, after fasting for 48 h develop convulsions soon after refeeding. The present study was performed to evaluate whether mice also develop convulsions after being deprived of food for 1–24 h. The effect of day–night fasting on the development of convulsions was also determined in 12-h deprived animals. Mice were deprived of food for periods of 1, 2, 3, 6, 9, 12, 18, 24, and 48 h. Animals fasted for 12 h during the day or night were deprived of food at 08:00 or 20:00 h, respectively. At the time of testing, animals were treated with intraperitoneal (i.p.) saline or 3 mg/kg scopolamine. Twenty minutes later, they were given food and allowed to eat ad lib. All animals were observed for 30 min for the incidence and onset of convulsions. Fasted animals treated with scopolamine developed clonic convulsions after food intake. Incidence of convulsions was significant in 2-, 3-, 12-, 18-, 24-, and 48-h deprived animals. Convulsions observed after deprivation of food for 12 h during the day or at night were almost similar in both regimens. Our results indicate that food deprivation itself, rather than its duration, seems to be the principal factor in the development of these convulsions.     

The effects of putative 5-hydroxytryptamine receptor active agents ond-amphetamine self-administration in controls and rats with 5,7-dihydroxytryptamine median forebrain bundle lesion

Animals in which 5,7-dihydroxytryptamine (5,7-DHT) was bilaterally injected into the median forebrain bundle (MFB) and sham lesioned animals were allowed access to an apparatus which delivered, upon lever pressing, intravenousd-amphetamine injections. MFB lesioned rats achieved stable self-injections patterns and self-administered more drug per test session than controls. A number of agents known to either directly or indirectly affect 5-hydroxytryptamine (5-HT) receptor function were administered prior tod-amphetamine access. The responses to these pretreatments in lesioned vs non-lesioned rats were markedly different. Pretreatment withl-tryptophan reduced the number ofd-amphetamine self-injections in sham lesioned rats but had no effect in MFB lesioned animals. Fluoxetine pretreatment, likewise, reduced responding in non-lesioned rats and had no observable effect in lesioned animals. Quipazine markedy reduced self-injection in control rats but was not evaluated in the lesioned group. The putative 5-HT antagonists utilized, cyproheptadine and methysergide, unpredictably reduced self-injection frequency of non-lesioned animals in a dose related manner. When MFB lesioned animals were pretreated with cyproheptadine, rapid bursts of lever pressing were observed and 3 of 6 animals thus treated died as a result (presumably amphetamine overdose). In the remaining animals, methysergide produced a similar marked increase in self-injection rate. While these data may suggest that, in some instances, non-serotonergic mechanisms are involved, for the most part it would appear that 5-HT containing neurons are of major import in some aspect ofd-amphetamine self-administration.     

Distribution and constitutional changes of edema fluid in cytotoxic brain edema analyzed by electron microscopy and differential scanning calorimetry

To understand the pathogenesis of brain edema, we studied distribution and constitutional changes of brain-tissue water by morphological and thermoanalytical methods in cytotoxic brain edema induced by 6-aminonicotinamide (6-ANA). Ninety-two Wistar rats were divided into three groups; Group I rats receiving physiological salt solution intraperitoneally served as controls. Group II and III animals were intraperitoneally given 120 mg/kg and 36 mg/kg of 6-ANA respectively. All animals were starved after injection of drugs to exclude differences in water intake. Then they were decapitated at 3, 6, 12, 24, 36 or 48 hours to measure specific gravity (SG) of large brain tissue (1.1-1.5 g), and to evaluate water content (WC) and free water ratio (FWR) of small brain-tissue samples (15-35 mg) taken from the frontal cortex; WC was measured by a drying-weighing method, and FWR was analyzed with a differential scanning calorimeter. Moreover morphological changes of the frontal cortex of the brain were studied in Group II (n = 12) at 3, 6, 12, 24 and 48 hours with an electron microscope. Neurological status of animals administered 6-ANA (Group II and III) deteriorated with time. Morphological studies showed that perivascular astrocytes and astrocytic processes in the cerebral cortex were swollen most remarkably at 48 hours. However neuronal and endothelial cells were almost intact. The FWR of Group I decreased significantly about four per cent (p less than 0.001) after being starved for 48 hours. But the SG and WC of the group showed little change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prior experience on bar-pressing in rats without neocortex

Rats in which all neocortex had been surgically removed produced similar patterns of performance to those previously established for rabbits with total neocortical ablations in a bar-pressing task for food reward. The animals deprived of neocortex developed inefficient patterns of food-tray related behaviours and a limit to their bar-pressing performance for intermittent rewards in the region of 4–10 presses per reward. The lesioned animals were also unable to form a sequential brightness discrimination on a GO-NOGO schedule using a bar-press response. Neither prior experience of other instrumental learning situations nor experience of working in the same apparatus and using the same instrumental response were sufficient to improve subsequent bar-press performance for intermittent reward in the neocortically lesioned animals. Previous success in improving such performance by pretraining procedures designed to facilitate identification of the part of the apparatus to be manipulated by the animal cannot easily be explained, therefore, on the basis of such incidental factors as increased behavioural sophistication or of increased familiarity with the apparatus and the instrumental response itself. The data are consistent with the view that the neodecorticate's difficulty in the bar-pressing situations for intermittent rewards is due to inadequate identification of cues associated with the object to be manipulated rather than to an associative learning deficit.     

The effects of putative 5-hydroxytryptamine receptor active agents on D-amphetamine self-administration in controls and rats with 5,7-dihydroxytryptamine median forebrain bundle lesions

Animals in which 5,7-dihydroxytryptamine (5,7-DHT) was bilaterally injected into the median forebrain bundle (MFB) and sham lesioned animals were allowed access to an apparatus which delivered, upon lever pressing, intravenous D-amphetamine injections. MFB lesioned rats achieved stable self-injections patterns and self-administered more drug per test session than controls. A number of agents known to either directly or indirectly affect 5-hydroxytryptamine (5-HT) receptor function were administered prior to D-amphetamine access. The responses to these pretreatments in lesioned vs non-lesioned rats were markedly different. Pretreatment with L-tryptophan reduced the number of D-amphetamine self-injections in sham lesioned rats but had no effect in MFB lesioned animals. Fluoxetine pretreatment, likewise, reduced responding in non-lesioned rats and had no observable effect in lesioned animals. Quipazine markedly reduced self-injection in control rats but was not evaluated in the lesioned group. The putative 5-HT antagonists utilized, cyproheptadine and methysergide, unpredictably reduced self-injection frequency of non-lesioned animals in a dose related manner. When MFB lesioned animals were pretreated with cyproheptadine, rapid bursts of lever pressing were observed and 3 of 6 animals thus treated died as a result (presumably amphetamine overdose). In the remaining animals, methysergide produced a similar marked increase in self-injection rate. While these data may suggest that, in some instances, non-serotonergic mechanisms are involved, for the most part it would appear that 5-HT containing neurons are of major import in some aspect of D-amphetamine self-administration.     

Tonic and phasic alteration in amygdala 5-HT, glutamate and GABA transmission after prefrontal cortex damage in rats

The relationship between the ventromedial prefrontal cortex and the amygdala during the presentation of an unconditioned fear stimulus was assessed. Rats underwent bilateral ibotenic acid or vehicle administration into the ventromedial prefrontal cortex. Five weeks later, the behavior as well as the neurochemical changes in the amygdala was evaluated before and after a brief cat presentation. Lesioned animal freezing behavior increased 10 times when compared to controls. In the right basolateral amygdala, basal concentrations of 5-HT, 5-HIAA, glutamate and serine were elevated but basal level of GABA was diminished in lesioned animals relative to controls. Sham but not lesioned animals increased 5-HT and decreased GABA and serine levels after cat presentation. Phasic changes in glutamate were not detected either in lesioned or shams but the difference in amygdala glutamate between lesioned and shams persisted after cat presentation. These data show that increased serotonin and glutamate tone and decreased gabaergic tone in the amygdala correlate to elevated fear and anxiety after prefrontal cortex ibotenic acid lesion. The lesion also seems to produce a failure of adaptive changes in neurotransmitter systems revealing lost of control of the ventromedial prefrontal cortex over the amygdala in frightening situations.     

Medial basal hypothalamic monoamine activity associated with intracerebroventricular p-chlorophenylalanine-induced hyperphagia

There is evidence for reciprocal interactions between the brain monoamine neurotransmitters serotonin and noradrenaline which may play a critical role in homeostasis. The aim of the present study was to establish the effect of drug-induced damage to the serotoninergic system on noradrenergic activity in the hypothalamus. Bilateral intracerebroventricular injections of p-chlorophenylalanine (PCPA; 3 mg/kg in 2 x 6 microliters) were made to induce destruction in the serotoninergic system. Relative to saline-injected controls, PCPA-injected rats began overeating by 3 days postinjection. On day 10, when the experimental rats were consuming approximately 120% that of controls, animals were 4-h food deprived, sacrificed and the medial basal hypothalamus was removed for later analysis (by gas chromatography/mass spectrometry) of noradrenaline (NA), serotonin (5-HT) and dopamine (DA) and their principal metabolites dihydroxyphenylethyleneglycol (DHPG), 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC), respectively. The ratio of metabolite to monoamine provided an index of functional activity. Trunk blood was collected for analysis of serum insulin and glucose. PCPA-injected animals had higher levels of DHPG (P less than 0.05), an increase in the DHPG/NA ratio (P less than 0.02), lower serum insulin (P less than 0.05) and increased serum glucose (P less than 0.05). There were significant correlations between noradrenergic activity (DHPG/NA ratio) and: (1) food intake (day 9 and 10 average; r = 0.62, P less than 0.05); and (2) serum glucose (r = 0.59, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavioral and morphological effects of minocycline in the 6-hydroxydopamine rat model of Parkinson's disease

The neuropathology in many neurodegenerative diseases is mediated by inflammatory cascades that influence neuronal dysfunction and death. Minocycline reduces the neurodegeneration observed in various models of Parkinson's. We exploited the unilateral 6-hydroxydopamine (6-OHDA) lesion model to assess the effect of minocycline on related neurodegeneration. Thirty Fisher 344 rats were divided into three daily treatment groups: (1) after: 45 mg/kg of minocycline beginning 24 h after lesioning; (2) before: 45 mg/kg of minocycline beginning 3 days before 6-OHDA lesioning; (3) control: corresponding saline-treated controls. Animals were assessed for apomorphine-induced rotations for 4 weeks. A longitudinal model for repeated measures showed that both after and before groups had significantly lower rotations than controls (P < 0.001 for both comparisons). Pair-wise group comparisons showed that the before animals rotated less compared to controls (mean rotations: 164 +/- 38 versus 386 +/- 49, respectively, P = 0.001). After animals also rotated significantly less then controls (mean rotations: 125 +/- 41 versus 386 +/- 49, respectively, P < 0.001). Animals receiving minocycline displayed reduced tyrosine hydroxylase-positive cell loss in the lesioned nigra versus contralateral nonlesioned nigra, compared to controls (mean differences: 5065 for after, 3550 for before, and 6483 for controls; P = 0.158 for after versus controls, P = 0.019 for before versus controls). The remaining lesioned nigral cells of both minocycline-treated groups were larger than controls, with the most robust cell size and fiber density observed in the after group. These data suggest that the therapeutic potential of minocycline may depend on the time of drug administration relative to neuropathogenic event.     

Mesencephalic lesions followed by normophagia but decreased body weight

Twenty mature male Sprague-Dawley rats were lesioned in the area of the ascending ventral noradrenergic bundle in the mesencephalon. Nine sham-operated animals served as controls. Food intake between the lesioned and nonlesioned groups was not significantly different except for the first day post surgery. However, body weight of the lesioned group was significantly below that of the controls when measured 15 days after the operation. The lesioned animals weighed significantly less than the controls throughout the rest of the experiment. They also were hypoactive when compared to the sham-operated rats. Control rats and lesioned rats did not differ significantly in deep rectal temperature. It is suggested that the significant decrease in body weight of the lesioned rats in the presence of normophagia may be caused by alterations in the animal's metabolism.     

Immunomodulatory actions of central ghrelin in diet-induced energy imbalance

We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1β, IFN-γ) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1β, IL-6, IFN-γ, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-β remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 μg/day) for five consecutive days significantly reduced TNF, IL-1β and IFN-γ levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of IFN-γ, IL-17, IL-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways.     

Control of food delivery in food-deprived rats mediates analgesia.

An experiment was carried out to investigate the effects of control of food delivery, in food-deprived rats, on analgesia. Tail flick latency was used as an index of pain sensitivity and naloxone reversibility of analgesia was used as the criterion for opioid involvement. Food-deprived rats were submitted to one of two schedules of food delivery. The 'contingent' group could control the delivery of food by lever-pressing. The 'non-contingent' group received the same number of food pellets but delivery of food was independent of lever-pressing behaviour. Animals in the 'control' group were placed in the test chamber but did not receive any pellets. Subjects were tested on 6 consecutive days, each test session being of 10 min duration. Half of the animals in each group received an intraperitoneal injection of saline (0.5 ml) prior to each test session, the other half received an intraperitoneal injection of naloxone (5 mg/kg in 0.5 ml saline) prior to each session. Both contingent and non-contingent food delivery resulted in a significant post-test analgesia. The analgesia was noticeably greater when food delivery was non-contingent and this analgesia was reversible by naloxone. The findings suggest that non-contingent food delivery, in food-deprived rats, elicits an opioid analgesia, whilst contingent food delivery elicits a non-opioid analgesia.