Biomedical subjects
M S Fanselow
Publications and source records attributed to M S Fanselow.
Naloxone and shock-elicited freezing in the rat.
The freezing behavior of the rat that occurs following painful electric shock was found to increase when the animal was pretreated with the opiate antagonist naloxone. Freezing was a positive linear function of drug dose and shock intensity (Experiment 2). Naloxone pretreatment enhanced freezing only when the animal was given two or three shocks but did not affect freezing when the animal was given only one shock or not shocked at all (Experiments 3, 4, and 5). Naloxone must be present during shock, nor just during the observation period, in order to increase freezing (Experiment 6). These results suggest that when an animal is shocked, it releases endogenous analgesics (endorphins) that make a subsequent shock less aversive. Naloxone, by blocking the endorphin system, makes the shock more aversive than it would normally be.
Conditioned and unconditional components of post-shock freezing.
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[D-Ala2,Leu5,Cys6]enkephalin: short-term agonist effects and long-term antagonism at delta opioid receptors.
Four experiments were conducted. Two examined the in vivo short-term effects (less than 35 min) and two examined the in vivo long-term effects (greater than 2 days) of the synthetic enkephalin analogue, [D-Ala2,Leu5,Cys6]enkephalin (DALCE). In the short term, DALCE was found to produce analgesia and transient immobility after intracerebroventricular (ICV) administration. We found a dose-related increase in paw-lick latency for rats placed on a hotplate (52 degrees C). In the second experiment, we determined that immobility was attenuated by pretreatment with naltrexone methobromide (QNTX, 0.1 microgram), and the delta selective antagonist, 16-methyl cyprenorphine (M80, 5 micrograms). QNTX and M80 significantly attenuated DALCE-induced immobility by more than 50% of control. Paw-lick latency was then measured on the hotplate to assess analgesia. Pretreatment with M80 reliably attenuated the DALCE-induced analgesia. Whereas QNTX failed to reliably attenuate paw-lick latency on the first trial, it was as effective as M80 on the second trial. We suggest that the short-term agonist effects of DALCE are produced by actions at mu and delta opioid receptors as would be predicted from prior in vitro studies showing moderate to high affinity, respectively, at these receptors. In the third experiment, DALCE was shown to display long-term behavioral antagonism that was selective for the delta receptor. Rats were injected ICV with 6.7 micrograms of DALCE and tested 48 hr later. Analgesia was measured by injecting 15% formalin subcutaneously followed 20 min later by an ICV injection of one of three selective opioid agonists (DAGO, DPDPE or U50488H).(ABSTRACT TRUNCATED AT 250 WORDS)
Differential effects of selective opioid peptide antagonists on the acquisition of pavlovian fear conditioning.
Pretreatment with opioid antagonists enhances acquisition of Pavlovian fear conditioning. The present experiments attempted to characterize the type of opioid receptor responsible for this effect using a procedure that assessed the fear of rats to a chamber previously associated with electric shock (1 mA, 0.75 s). Freezing, a species-typical immobility, was employed as an index of fear. Two mu opioid antagonists, CTOP (40 ng) and naloxonazine (10 micrograms), enhanced conditioning. On the other hand, the kappa antagonist nor-binaltorphimine reduced conditioning. Two delta antagonist treatments (16-methyl cyprenorphine and naltrindole) had no reliable effect on acquisition. Thus the enhancement of conditioning appears to be mediated by mu receptors. Previous research has shown that the conditional fear produced by these procedures caused an analgesia that is also mediated by mu receptors. It is argued that the enhancement effect occurs because of an antagonism of this analgesia and that the analgesia normally acts to regulate the level of fear conditioning.
Body temperature as a conditional response measure for pavlovian fear conditioning.
On six days rats were exposed to each of two contexts. They received an electric shock in one context and nothing in the other. Rats were tested later in each environment without shock. The rats froze and defecated more often in the shock-paired environment; they also exhibited a significantly larger elevation in rectal temperature in that environment. The rats discriminated between each context, and we suggest that the elevation in temperature is the consequence of associative learning. Thus, body temperature can be used as a conditional response measure in Pavlovian fear conditioning experiments that use footshock as the unconditional stimulus.