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M T Bardo

Publications and source records attributed to M T Bardo.

98 records · Page 6Linked to original sources

Opiate receptor ontogeny and morphine-induced effects: influence of chronic footshock stress in preweanling rats.

The ontogeny of opiate receptors was examined in various CNS regions of preweanling rats which received either daily inescapable footshock stress, exposure to a footshock apparatus without shock, or no handling from birth to 21 days of age. At 21 days of age, each of these treatment groups was also assessed for morphine-induced changes in activity, hot-plate paw-lick latency, and core body temperature. Marked regional differences in [3H]naloxone binding capacity were observed from 7 to 21 days of age in spinal cord, medulla-pons, midbrain, hypothalamus, striatum, and cortex. Caudal regions approached adult-like [3H]naloxone binding before rostral regions. The normal ontogeny of opiate receptors was not significantly influenced by the chronic footshock treatment. However, footshock treatment significantly reduced the efficacy of morphine (2 mg/kg) in producing hypoactive and antinociceptive effects, but not in producing a hyperthermic effect. These results demonstrate that stress-related changes in the behavioral efficacy of morphine do not necessarily depend upon changes in those opiate receptor populations that bind naloxone.

Aging↗

Shuttlebox avoidance by rats using white noise intensities from 90-120 db SPL as the UCS.

Hooded rats in 4 groups (10 M, 10 F each) were given shuttlebox avoidance training, 25 trials a day for 6 consecutive days, using a compound light-click warning signal and white noise as an aversive unconditioned stimulus at either 90, 100, 110, or 120 db SPL. Avoidance performance was an inverted U-shaped function of noise level. Females were significantly more active than males at each noise level, but although females performed more avoidance responses than males at each level, this sex difference was not significant. Avoidance response latencies were relatively invariant across training sessions for each group, as were escape responses latencies for the 100- and 110-db groups. Escape response latencies for the 90- and 120-db groups increased across training sessions. Shuttlebox performance as a function of increasing white noise UCS level is, in most respects, similar to performance obtained with increasing shock intensities.

Animals↗

Exposure to a nonfunctional hot plate as a factor in the assessment of morphine-induced analgesia and analgesic tolerance in rats.

Rats not exposed to a hot plate with or without morphine and later tested on the functional hot plate with or without morphine, displayed increased paw lick latency relative to same-injected rats given pretest hot plate exposure. This analgesic effect, was termed behavioral analgesia since it, unlike morphine-induced analgesia, was not reversed by naloxone (Experiment 2). Behavioral tolerance was evident in animals exposed to the nonfunctional hot plate regardless of drug treatment and was dissociated from pharmacological tolerance. Behavioral analgesia and tolerance reported here may involve habituation to novel distractive stimuli associated with the hot plate test environment.

Analgesia↗

Brief communication. Shock-elicited flight response in chickens as an index of morphine analgesia.

Morphine influence on a flight response elicited by wing shock was examined in 17-day-old chickens. The chickens received either morphine (30 mg/kg) or saline on two days and were tested for responsivity to wing shock 30 min after each injection. On a third day all chickens received saline injections and were tested again. Tests consisted of delivering wing shock at increasing intensity to determine the threshold of a species-typical flight response. Morphine significantly increased the flight response th reshold on the first test (analgesia), but not on the second test. Shock intensity values required to elicit the flight response in morphine and saline groups did not differ significantly on the third test when all birds received saline. In contrast to previous evidence, these results demonstrate morphine analgesia in chickens using a dose that approximates the analgesic dose range reported for other species.

Analgesia↗

Environmental enrichment attenuates locomotor sensitization, but not in vitro dopamine release, induced by amphetamine.

Rats were raised from weanling until young adulthood in either an enriched condition (EC) or isolated condition (IC). Following this, the locomotor and rewarding effects of amphetamine were determined using the conditioned place preference (CPP) paradigm. EC rats were more sensitive to the acute locomotor stimulant effect and rewarding effect of amphetamine relative to IC rats. In contrast, EC rats were less sensitive than IC rats to the locomotor sensitization effect obtained across repeated amphetamine injections. To determine the effect of environmental enrichment on alteration of brain dopamine (DA) function induced by amphetamine, the effect of amphetamine on electrically evoked release of DA and dihydroxyphenylacetic acid (DOPAC) was determined in vitro using tissue slices from the nucleus accumbens and striatum of EC and IC rats. No differences between EC and IC rats in release of DA or DOPAC were evident, suggesting that the environmentally induced difference in sensitivity to the behavioral effects of amphetamine involves a neural mechanism extrinsic to the mesolimbic and nigrostriatal terminal field regions.

3,4-Dihydroxyphenylacetic Acid↗

Impaired supersensitivity to morphine following chronic naltrexone treatment in senescent rats.

Chronic administration of opiate antagonists produces an increase in the density of opiate receptors, as well as an enhanced sensitivity to the analgesic and locomotor depressant effects of morphine. The present study assessed whether aging alters these regulatory processes. Young (3-4 months), middle-aged (10-11 months), and senescent (25-30 months) rats were implanted subdermally with slow-release naltrexone pellets or were given sham surgery. The pellets were removed 10 days later. Twenty-four hours after pellet removal, morphine-induced (5 mg/kg, SC) analgesia and locomotor activity were assessed. Young and middle-aged rats treated with naltrexone showed enhanced sensitivity to the analgesic and locomotor activity depressant effects of morphine relative to age-matched controls. In contrast, senescent rats treated with naltrexone did not differ from age-matched controls in their response to morphine. The density of opiate receptors labeled with 3H-naloxone was measured in the anterior striatum. Both young and senescent rats treated with naltrexone exhibited an increase in opiate receptor density relative to age-matched controls. The results indicate that senescent rats are capable of up-regulating opiate receptors following chronic naltrexone treatment but do not exhibit the corresponding functional supersensitivity to morphine.

Aging↗

Locomotor activity and dopamine synthesis following 1 and 15 days of withdrawal from repeated apomorphine treatments.

In two experiments, the effects of repeated apomorphine treatments on locomotor activity and terminal field dopamine synthesis was assessed after either a 1- or 15-day withdrawal period. In the first experiment, rats (n = 11/group) were treated with apomorphine (1.0 mg/kg, s.e.) or vehicle and tested for locomotor activity daily for 10 days. Fifteen days after the last repeated treatment, all rats received 1.0 mg/kg apomorphine and were tested for locomotor activity. Locomotor sensitization developed over the 10 day period and was still evident after the 15-day withdrawal period. In the second experiment rats (n = 11/group) were treated with apomorphine (1.0 mg/kg, s.c.) or vehicle and tested for locomotor activity daily for 10 days. Dopamine synthesis was assessed following 1 or 15 days of withdrawal by measuring dihydroxyphenylalanine (DOPA) accumulation (after DOPA decarboxylase inhibition with NSD-1015) in striatum and nucleus accumbens-olfactory tuberele. As in the first experiment, rats treated with repeated apomorphine showed locomotor sensitization over the 10 days, relative to controls. Dopamine synthesis was reliably enhanced in the striatum, but not nucleus accumbens-olfactory tuberele, following both 1- and 15-day withdrawal periods. These results indicate that enhanced basal dopamine synthesis following repeated apomorphine treatments, similar to locomotor sensitization, is a persistent phenomenon.

Animals↗

Up-regulation of opiate receptors following chronic naloxone treatment in aged rats.

The present study assessed whether there are age-dependent differences in up-regulation of opiate receptors following chronic naloxone treatment in mature (3 months) and aged (27 months) male Wistar rats. Half of each age group were implanted subdermally with slow-release naloxone pellets for 10 days, and half were given sham surgery. Twenty-four hours after pellet removal, the rats were decapitated and various CNS areas including spinal cord, hindbrain, midbrain, diencephalon, hippocampus, striatum, olfactory tubercles/nucleus accumbens and prefrontal cortex were dissected and assayed for [3H]naloxone binding. The results indicated that aged rats had fewer opiate receptors in the spinal cord, midbrain, striatum, and olfactory tubercle/nucleus accumbens. Despite this age-related decline in opiate receptors, aged rats showed an up-regulation response similar to mature rats in all areas except the hippocampus of the left hemisphere, where they showed enhanced up-regulation relative to mature rats. The maintained plasticity of the opioid system contrasts with findings in other receptors systems where age-related impairments of antagonist-induced up-regulation have been reported.

Aging↗