Richard Blair

Conditioned place preference: An evaluation of morphine's positive reinforcing properties

The place-preference paradigm was evaluated as a measure of morphines positive reinforcing properties. Previous place-preference studies obtained a morphine place preference of 26%–63%. In order to examine whether differences in procedure may account for this scatter, the present experiment investigated whether there is any difference in the absolute magnitude of preference when animals are conditioned on their non-preferred side of the box or when animals are randomly assigned to the side of conditioning. Furthermore, the number of conditioning days was extended with 3 intervening test days, and drug doses were doubled following each test day. The results showed no significant difference between conditioning animals on their non-preferred side or randomly assigning them to the side of conditioning. However, by extending the number of conditioning days, as well as by following the drug regimen used, the animals showed a greater magnitude of preference than that observed in previous studies. The implications of these findings for the usage of this paradigm as a measure of morphines positive reinforcing properties are discussed.

Explosive motor behavior, rigidity and periaqueductal gray lesions.

Abstract Rats lesioned in the periaqueductal gray (PAG) manifested explosive motor behavior (EMB) shortly after surgery. When tested 24 hours postsurgery, these animals failed to exhibit the usually observed EMB in response to an intraventricular infusion of morphine. In contrast, the lesions did not interfere with the ability of intraventricularly infused etonitazene to produce rigidity. The results suggest that the site of action for morphine-produced EMB is in the PAG and that the neural substrates for EMB and rigidity are, at least in part, anatomically distinct.

OPIATE RECEPTORS MAY MEDIATE THE SUPPRESSIVE BUT NOT THE EXCITATORY ACTION OF ACTH ON MOTOR ACTIVITY IN RATS

Subcutaneous injections of adrenocorticotropin (ACTH) or of the opiate antagonist naltrexone produced a one (2.0 mg/kg) dpressed, whereas smaller doses of ACTH (50 micrograms/kg) and of naltrexone (0.125 and 0.25 mg/kg) stimulated motor activity in the open field test. Furthermore, naltrexone at a dose level that had no effect on motor activity blocked the suppressive effect of the high doses of ACTH but had no effect on the stimulating effect of the intermediate dose of ACTH. Finally, chronic naltrexone administration resulted in enhanced sensitivity to the suppressive but not to the stimulating effect of ACTH on motor activity. It is argued that opiate receptors may play a selective role in the effect of ACTH on motor activity. Such receptors may mediate the supressive effect of high doses of ACTH whereas other, naltrexone insensitive receptor systems may mediate the stimulating effect of ACTH on activity functions.

Naloxone's antagonism of rigidity but not explosive motor behavior: possible evidence for two types of mechanisms underlying the actions of opiates and opioids.

Rats received an intraperitoneal injection of naloxone prior to an intraventricular infusion of etonitazene or morphine. The rigidity produced by etonitazene was antagonized by naloxone (10 mg/kg). In contrast to the results of a previous study, all doses of naloxone up to 160 mg/kg failed to attenuate the explosive motor behavior resulting from an intraventricular infusion of morphine. The results of the present study indicate that all actions of opiates and opioids are not mediated by the naloxone-blocked opiate receptor.

Increased amphetamine potency following chronic naltrexone administration in rats.

Abstract Chronic administration of the long acting opiate antagonist naltrexone potentiated the amphetamine and apomorphine- -induced stimulation of locomotor activity in rats. Similar treatment also resulted in increased locomotor activity in saline injected rats. The results suggest that chronic opiate receptor blockade may lead to the development of supersensitivity in dopamine systems that mediate motor control. The results provide further support for the notion that endogenous opioids modulate the function of dopamine systems in the brain.

Stress-induced analgesia: A performance deficit or a change in pain responsiveness?

Two experiments were conducted in order to determine whether a performance deficit mediated stress-induced analgesia. In the first experiment, the effects of restraint stress and task difficulty on latency to escape from a hot plate were studied in rats. Statistical analysis of escape latencies revealed that restraint and task difficulty produced significant increases in escape latencies and that the interaction of restraint × task difficulty was not significant. The second experiment examined the effects of restraint on locomotor activity in an open field. Restraint did not have an observable effect on activity counts. The results of the two experiments suggest that the observed increases in escape latencies produced by restraint reflects a change in pain responsiveness and not a performance deficit.

Assimilation Theory, Attentive Fields, and the Müller—Lyer Illusion

The assimilation theory of geometric illusions was employed to predict changes in the outgoing and ingoing forms of the Müller—Lyer illusions as a function of attentive field size. It was found that the theory predicted correctly the form of the function relating amount of illusion and size of attentive field only for the outgoing Müller—Lyer. For the ingoing illusion the prediction was opposite to the empirically obtained results. The findings are seen as additional evidence for the untenability of a unitary theory, such as assimilation theory, for both versions of the Müller—Lyer illusion as they fail to account for substantial differences between them.

ACTH1–39 but not naltrexone produces biphasic effects on locomotor activity

Two experiments were conducted in order to investigate the effects of chronic ACTH and naltrexone treatment on motor activity in an open-field. In the first experiment, Wistar rats received two daily injections of either ACTH1-39-saline, naltrexone-saline, ACTH1-39-naltrexone or saline-saline for 24 consecutive days. Immediately following injections, motor activity was measured every fourth day. The results indicated that ACTH and naltrexone each had depressive effects on motor activity that did not dissipate over 24 days. In the second experiment, the procedure was similar to the first except that motor activity was measured at five hours postinjection. The results revealed that naltrexone by itself or in combination with ACTH had no observable effect on motor activity. ACTH was observed to have a stimulatory effect on motor activity that decreased over days and was not naltrexone reversible. The results are discussed in terms of different mechanisms underlying the effects of ACTH and naltrexone.

Heroin, but not levorphanol, produces explosive motor behavior in naloxone-treated rats

Intraventricular infusions of heroin (an opiate) or levorphanol (an opioid) in rats produced rigidity but not explosive motor behavior (EMB). When preceded by an IP injection of naloxone, infusions of heroin but not levorphanol produced EMB. The results suggest that naloxone-antagonized effects of opiates mask EMB and that certain opioids do not induce EMB.

Lithium and ion chelators mimicked morphine in the production of explosive motor behavior

Intraventricular infusions of lithium and ion chelators mimicked morphine in the production of explosive motor behavior (EMB). Naloxone (20 mg/kg) did not antagonize EMB. In vitro calcium assays indicated that only ion chelators directly interacted with calcium. The behavioral and the in vitro results indicate that although ion chelators may induce EMB as a function of their ability to bind ions, this is not the case for morphine and lithium.