PubMed Health⌕ Search

Biomedical subjects

M S Fanselow

Publications and source records attributed to M S Fanselow.

At least 73 records · Page 4Linked to original sources
PubMed1988

Peripheral versus intracerebroventricular administration of quaternary naltrexone and the enhancement of Pavlovian conditioning.

When rats are placed in a context with mild electric shock (1 mA/0.75 s), the environmental cues alone can provoke an immobile crouching behavior termed freezing. Freezing response is a Pavlovian conditional response provoked by stimuli that come to be associated with shock. Previous research has shown that peripheral injection of opioid antagonists can enhance this response. Two experiments were conducted to determine if peripheral and/or central opioid mechanisms are involved in this enhancement of freezing by employing quaternary naltrexone (QNTX), an opioid antagonist which does not readily penetrate the 'blood-brain barrier'. QNTX (5 and 10 micrograms/rat) administered i.c.v. prior to shock significantly enhanced freezing 24 h later, whereas i.p. injected QNTX, at doses as high as 20 mg/kg, had no effect. These results suggest that the enhancement of conditional freezing produced by QNTX is mediated by central, not peripheral, opioid mechanisms.

Animals↗
PubMed1988

Ethylketocyclazocine and bremazocine analgesia in neonatal rats.

In three experiments we examined the analgesic potency of kappa opioid receptor agonists in 2- and 16-day-old rats. Ethylketocyclazocine (1-50 mg/kg) produced similar dose- and time-dependent increases in the latency to retract a hind paw from a noxious thermal stimulus in rats of both ages. Bremazocine (0.001-10 mg/kg), a kappa agonist with reported antagonist activity at mu receptors, was also effective in producing analgesia in 2-day-old rats. The dose-effect relationship for bremazocine was nonmonotonic. Bremazocine analgesia (0.1 mg/kg) was reversed by both naltrexone and MR2266, a putative kappa opioid antagonist. These results are discussed in terms of the functional integrity of a kappa analgesic system in the developing rat.

Analgesia↗
PubMed1988

The ontogeny of opiate tolerance and withdrawal in infant rats.

The acquisition of morphine analgesic tolerance was investigated in neonatal rats. Morphine was found to produce a potent analgesia, as measured by latency to retract a hindpaw from a 52 degree C hotplate, in rat pups as young as 1 day of age. Morphine analgesic tolerance, however, did not develop in rats until the third week of life. Rats given the same daily morphine regimen starting at 15 days of age or older showed rapid tolerance development. The data from four experiments indicate that experience with morphine prior to this age (Day 15) does not impact on the analgesic efficacy of the drug. Similarly, when morphine treatment was discontinued and the rats given a naloxone challenge, withdrawal symptoms were not observed in very young rats. Opiate withdrawal was first detected in rats that started their daily morphine treatment at 30 days of age and were then challenged with naloxone at 52 days of age. Therefore, two correlates of opiate addiction, tolerance and withdrawal, appear to be relatively late-developing phenomena in the rat.

Age Factors↗
PubMed1988

Conditional analgesia, defensive freezing, and benzodiazepines.

When rats are placed in a situation that has come to be associated with footshock through the process of Pavlovian conditioning, they react with the species-specific defensive response of freezing and a reduction in sensitivity to painful stimulation. In the present experiments, the effects of three benzodiazepines on both of these responses were examined. Pain sensitivity was measured with the formalin test. Concurrent observations of formalin-induced recuperative behavior and freezing were recorded while the animals were in the presence of shock-associated contextual stimuli. It was found that midazolam (Experiments 1 and 2), chlordiazepoxide (Experiment 3), and diazepam (Experiment 4) were capable of significantly attenuating the conditional analgesia. Midazolam and diazepam also reduced the freezing response. The finding that these anxiolytic agents attenuate both conditional responses suggests that the freezing and analgesia are mediated by a common fearlike process.

Animals↗
PubMed1988

Changes in feeding and foraging patterns as an antipredator defensive strategy: a laboratory simulation using aversive stimulation in a closed economy.

The effects of the risk of electric shock on the meal patterns of rats living in an operant chamber were investigated. Rats could obtain food by working on a response lever that provided reinforcement according to chained fixed-ratio continuous reinforcement schedules that allowed the animals control over meal size. Using a two-compartment operant chamber with a safe nesting area and manipulanda area with a grid floor, shock could be correlated with responding on the schedule. Shocks (less than or equal to 1.25 per hour) were scheduled to occur randomly throughout the day, independent of the rat's behavior. Shock caused a reorganization of meal patterns such that the animals took less frequent but larger meals. This pattern reduced the time the animals spent at risk without compromising caloric balance. Similar changes in feeding pattern were obtained in both hooded and albino rats. Exposure to shock in a separate chamber did not produce these behavioral modifications. The magnitude of shock-induced alterations of meal patterns was greater with chained fixed-ratio 90 continuous reinforcement than with chained fixed-ratio 10 continuous reinforcement. Additionally, the rats seemed to be able to reduce food intake but increase caloric efficiency, such that the reduced food intake did not have deleterious effects on maintenance of body weight. These behavioral modifications reduced the number of shocks received from that which would have been expected if meal pattern changes had not occurred. We suggest that this technique may provide a useful laboratory simulation of the impact that the risk of predation has on foraging behavior.

Animals↗
PubMed1988

Contextual conditioning with massed versus distributed unconditional stimuli in the absence of explicit conditional stimuli.

Rats received unsignaled shocks in an observation chamber, with different groups varying with respect to time between shocks. Twenty-four hours later the rats were returned to the observation chamber for a test of conditioning to contextual stimuli. The freezing response served as the dependent variable. In Experiment 1 we found that distributed shock trials (60 s) resulted in more context conditioning than did massed trials (3 s or 16 s). Experiment 2 replicated this intertrial interval (ITI) effect when total time in the context was equated for the massed and distributed groups. The observed beneficial effect of distributed practice for conditional stimuli arises because of decreased contextual conditioning with longer ITIs (e.g., Gibbon & Balsam, 1981; Rescorla & Wagner, 1972). Although the basic effect of enhanced performance with longer ITIs is consistent with Wagner's rehearsal model (e.g., 1978), three findings argue against such an account. First, posttrial stimulation did not reduce the benefit obtained from distributed trials (Experiment 3). Second, intertrial distractors did not improve performance of the animals subjected to massed trials (Experiment 4). And third, the ITI effect was not eliminated when conditioning was brought to its asymptote (Experiment 5). The overall pattern of data is consistent with an opponent-process account suggesting that in addition to supporting conditioning, the unconditional stimulus (US) activates a B-state capable of reducing the impact of the next US and that this B-state lasts longer than 16s but decays before 60 s.

Animals↗
PubMed1987

Central and peripheral injection of quaternary antagonist, SR58002C, reduces drinking.

Earlier research has demonstrated that opioid involvement in drinking is primarily mediated centrally [8,10]. Drinking is attenuated by the centrally and peripherally active opioid antagonists naloxone and naltrexone in doses as low as 1.0 mg/kg, but not by the quaternary forms of these antagonists [4]. Peripherally administered quaternary forms of these antagonists fail to suppress drinking in doses as high as 10 mg/kg. We generated dose-response curves for centrally and peripherally administered SR58002C, a "newer" quaternary opioid antagonist purported to have high peripheral selectivity, on drinking in 23.5 hr water deprived rats. SR58002C was administered both intracerebroventricularly (ICV, 0, 10, 40 and 80 micrograms/rat) and intraperitoneally (IP, 0, 10, 40 and 80 mg/kg). Doses of SR58002C above 10 mg/kg IP or 10 micrograms ICV significantly reduced drinking in comparison to controls. However, SR58002C appears to be less potent than quaternary naltrexone in suppressing drinking after ICV administration.

Animals↗
PubMed1987

Effects of cerebellar vermal lesions on species-specific fear responses, neophobia, and taste-aversion learning in rats.

The cerebellar vermis has extensive anatomical connections with many brain stem and forebrain structures which have been implicated in emotional or affective behavior. Previous reports indicate that lesions of the vermis in a variety of experimental animals result in altered emotional behavior. The studies reported here attempted to clarify the nature of the change in emotional behavior following vermal lesions in rats by testing the animals in a variety of fear-eliciting situations. As compared with controls, vermal-lesioned rats froze less in the presence of a cat and showed fewer signs of fear in an open field. However, their responses to footshock did not differ fundamentally from controls. They recovered more quickly than controls from the neophobic response to a novel taste but showed robust taste-aversion learning. The results are discussed in terms of the role of the cerebellum in the modulation of fear-related behaviors and in terms of similarities and differences with the effects of amygdala lesions. The results expand the body of data implicating the cerebellum in the modulation of complex motivational behavior.

Animals↗
PubMed1987

Effects of naltrexone on learning and performance of conditional fear-induced freezing and opioid analgesia.

In the presence of Pavlovian conditional aversive stimuli rats engage in defensive freezing and exhibit a decreased sensitivity to painful stimulation. Administration of the opioid antagonist naltrexone (7 mg/ml/kg) prior to training in a context fear conditioning procedure using footshock caused an increase in freezing but did not affect suppression of formalin-induced recuperative behaviors relative to controls during a test session 24 hr later. The same dose of naltrexone given during the test session reversed conditional analgesia without altering the level of freezing. These results suggest that full expression of endogenous opioid analgesia during training is not necessary for conditional responding.

Animals↗
PubMed1987

Quaternary naltrexone reveals the central mediation of conditional opioid analgesia.

Earlier research has demonstrated that when rats are placed in a context associated with mild electric shock (1 mA/0.75 sec), environmental cues alone can produce conditional analgesia that suppresses pain sensitivity on the formalin test. This analgesia appears to be mediated by endogenous opioids since it is reversed by the centrally active opioid antagonists naloxone and naltrexone. Two experiments attempted to determine if peripheral or central opioids mediate this analgesia by employing quaternary naltrexone (QNTX), an antagonist which does not readily penetrate the blood-brain barrier at moderate doses. Intracerebroventricularly administered QNTX (10 micrograms) significantly reversed conditional analgesia, whereas intraperitoneally injected QNTX did not affect formalin-induced behavior. These results suggest that the conditional analgesia produced by our procedures is mediated by central, not peripheral, opioid mechanism(s).

Animals↗
PubMed1987

Strain differences in reversal of conditional analgesia by opioid antagonists.

The ability of both naloxone and naltrexone to block conditional analgesia produced by shock associated contextual stimuli was determined using rats from three suppliers. Naltrexone (7 mg/kg) was equally effective in reversing analgesia on the formalin test in all rats tested. Naloxone (7 mg/kg) significantly affected analgesia in Long-Evans and Holtzman Sprague-Dawley rats but had no effect on Charles River (CD) Sprague-Dawley rats. Charles River rats also differed from the other groups in the amount of time spent freezing to apparatus cues. These results indicate that genetic factors and the choice of antagonists may complicate distinctions between opioid and nonopioid analgesia.

Analgesia↗
PubMed1986

Species-specific danger signals, endogenous opioid analgesia, and defensive behavior.

The effects of handling stimuli and stress odors on species-specific defensive behavior and pain sensitivity were examined in rats. Animals not adapted to handling had longer jump latencies on the hot plate test of pain sensitivity than those with extensive handling experience. In a postshock freezing test, naltrexone enhanced defensive freezing relative to saline controls in nonadapted animals. However, naltrexone produced no such effect in rats that were adapted to handling. These two studies indicate that the handling procedure triggered an endogenous opioid analgesic response in rats not adapted to handling. Experiment 3 showed that a similar naltrexone-reversible opioid analgesia can be triggered by stress odors. Naltrexone, when compared to saline, enhanced postshock freezing in the presence of conspecific stress odors, but not in their absence. In Experiment 4, stress odors and nonadapted handling were able to activate defensive freezing directly, when tested in compound but not in isolation. The studies are consistent with the view that stress odors and handling stimuli are danger signals that activate endogenous opioid analgesia as well as defensive behavior, suggesting that analgesia is a component of the rat's defensive behavior system.

Adaptation, Psychological↗
PubMed1985

Odors released by stressed rats produce opioid analgesia in unstressed rats.

When unstressed rats were placed in a chamber containing the odor of a conspecific that had received electric shock, they became analgesic as assessed by the formalin test. The odors of nonstressed conspecifics and novel odors produced no such effect. This analgesia was reversed by naltrexone. The data suggest that naturalistic stimuli innately associated with aversive environmental events can activate endogenous pain control mechanisms.

Animals↗
PubMed1985

Exposure to a cat produces opioid analgesia in rats.

Two experiments were conducted to test the prediction that rats should react with reduced sensitivity/reactivity to nociceptive stimulation in the presence of a cat. In Experiment 1, naloxone or saline was administered, and rats were exposed to no stimulus, a novel stimulus, or a cat. In Experiment 2, rats were exposed to either no stimulus or a cat, and naltrexone was administered. In both experiments, rats tested in the presence of the cat showed a significant reduction in sensitivity/reactivity to a skin-irritating formalin injection. Naltrexone reversed this analgesia.

Animals↗
PubMed1984

Shock-induced analgesia on the formalin test: effects of shock severity, naloxone, hypophysectomy, and associative variables.

Rats were exposed to three shocks, spaced 20 s apart, at two different levels of severity, low (.75 s, 1 mA) and high (3 s, 4 mA). Both shock levels produced a similar suppression of the recuperative behavior elicited by an injection of formalin into a rat's hind paw. Naloxone fully reversed the analgesia produced by the low-severity shock but only partially reversed the analgesia produced by the high-severity shock (Experiment 1). Hypophysectomy did not alter the level of analgesia (Experiment 2). When the rats were tested in a chamber different from the one they were shocked in, both analgesias were totally reversed (Experiment 3). However, imposing a delay between shock and analgesia testing did not reduce analgesia (Experiment 4). These results suggest that analgesia is not directly elicited by the shock but by apparatus stimuli associated with shock. Further support for this position was obtained when it was found that a Pavlovian extinction procedure could completely eliminate analgesia (Experiment 5). In all of the experiments, the freezing response, one of the rat's species-specific defense reactions, was monitored simultaneously with recuperative behavior. A parallel was found between analgesia and this defensive response, a result suggesting that an animal's endogenous analgesic systems may be activated along with the animal's defensive motivational system. The results point to the critical nature of associative variables in the control of endogenous analgesic systems. They also suggest that shock severity is a determinant of analgesia's sensitivity to naloxone.

Animals↗
PubMed1984

Opiate modulation of the active and inactive components of the postshock reaction: parallels between naloxone pretreatment and shock intensity.

Electric footshock elicited an immediate burst of activity followed by a period of immobility termed freezing. Naloxone, an opiate antagonist, enhanced both of these postshock reactions (Experiment 1). Naloxone's effects on the active and inactive components of the postshock reaction paralleled those of increasing shock intensity (Experiment 2). This finding suggests that the drug caused these results by enhancing the perceived intensity of shock. The facilitatory effects of naloxone on the active and inactive reactions to shock appear to be specific to nociceptive stimuli, as naloxone decreased the activity burst elicited by a nonnociceptive startling stimulus and had no effect on the freezing that followed that nonnociceptive stimulus (Experiment 3). Naloxone could accomplish its alteration of perceived intensity by antagonizing endogenous opioid analgesic systems. However, as hypophysectomy did not block the drug's action, the effects are not mediated by pituitary opioids (Experiment 4).

Animals↗