Stimulation of abducens nucleus supports classical conditioning of the nictitating membrane response.

The acquisition and terminal performance of a classical conditioning group compared with a control group indicated that extension of the nictitating membrane elicited by direct electrical stimulation of the abducens nucleus was successfully conditioned to a previously neutral stimulus. The conditioning so obtained was associative and not due to such nonassociative factors as sensitization, pseudo-conditioning, or alteration in base-rate responding.

Morphine's effects on differential serial compound conditioning and reflex modification of the rabbit's (Oryctolagus cuniculus) nictitating membrane response.

This study sought to determine the effects of morphine (0, 2, and 5 mg/kg) on (a) differential classical conditioning of the rabbit's (Oryctolagus cuniculus) nictitating membrane response (NMR) to the serial compounds A-X-unconditioned stimulus (US) and B-X-US (Experiment 1) and (b) the reflex modification effects of the compounds and their components (Experiment 2). These experiments determined specifically morphine's effects on the distinctiveness and time course of stimulus representations by examining morphine's dose-response effect on (a) differential responding to A and B and their conditional control over responding to X within the compounds and (b) the unconditioned excitatory effects of the compounds and their components as assessed by their ability to modify the amplitude of the unconditioned NMR. The results of these experiments indicate that morphine, in a dose-dependent manner, can operate to profoundly attenuate the distinctiveness and persistence (short-term memory) of stimulus representations.

Electrical stimulation of brainstem nuclei: elicitation, modification, and conditioning of the rabbit nictitating membrane response.

Electrical stimulation of the reticular formation, pars oralis of the spinal trigeminal, abducens, and accessory abducens nuclei was used to assess the role of these sites in the elicitation, reflex modification, and classical conditioning of the rabbit's nictitating membrane response (NMR). Although electrical brain stimulation of the targeted sites revealed comparable levels of unconditioned responses, the spinal trigeminal nucleus was the only site at which reflex modification and conditioned response acquisition occurred reliably. These findings suggest that a locus of conditioned stimulus and unconditioned stimulus interaction, mediating either or both reflex modification and NMR conditioning, is on the sensory side of the reflex arc, at the pars oralis of the spinal trigeminal nucleus.

Effects of morphine, ethylketocyclazocine, and N-allylnormetazocine on classical conditioning of the rabbit nictitating membrane response.

The rabbit's nictitating membrane response was classically conditioned to tone and light conditioned stimuli presented for 800 ms before delivery of a 100-ms unconditioned shock stimulus. Both the mu receptor agonist morphine (5 mg/kg) and the kappa receptor agonist ethylketocyclazocine (1 mg/kg) significantly retarded the acquisition of conditioned responses (CRs). The retardant effects of both morphine and ethylketocyclazocine on CR acquisition could still be detected when the rabbits were tested 5 days after cessation of drug injections. At the dose employed in this study (5 mg/kg), the sigma receptor agonist N-allylnormetazocine had no effect on acquisition. The retardant effects of morphine and ethylketocyclazocine on acquisition were significantly antagonized by both naloxone (1 mg/kg) and N-allylnormetazocine (5 mg/kg). It was suggested that mu and possibly kappa receptors are involved in the retardant effects of opiates on the acquisition of classically conditioned responses.

Elicitation, modification, and conditioning of the rabbit nictitating membrane response by electrical stimulation in the spinal trigeminal nucleus, inferior olive, interpositus nucleus, and red nucleus.

Elicitation of responses by electrical brain stimulation (EBS) was related to the synaptic distance of the target nucleus from the accessory abducens. Specifically, responses to EBS in the spinal trigeminal nucleus (TRIG) and red nucleus (RN) increased as a positive function of stimulation parameters. Responding to EBS in the interpositus nucleus (IP) was lower, and responding to EBS in the inferior olive (IO) was negligible. EBS in the TRIG, IP, and RN nuclei was then paired with a tone conditioned stimulus (CS). The CS modified responses for EBS in RN and TRIG but not IP. CS-EBS pairings yielded conditioned response (CR) acquisition, in which Groups TRIG, IP, and RN reached asymptotes of 90%, 70%, and 43% CRs, respectively. Thus, contrary to previous findings, EBS in the efferent pathway can support CR acquisition. The results are discussed with respect to the role of projections from the RN to the cerebellar cortex and the TRIG nucleus.

Sensory and associative effects of LSD on classical appetitive conditioning of the rabbit jaw movement response.

Three experiments were conducted to determine the effects of LSD (30 nmol/kg) in classical appetitive conditioning of the rabbit jaw movement response (JMR). In experiment 1, LSD significantly enhanced the acquisition of conditioned responses (CRs). The performance of control groups receiving unpaired presentations of the conditioned stimulus (CS) and unconditioned stimulus (UCS) demonstrated that LSD's enhancing effect on conditioning could not be attributed to an elevation in baseline responding, sensitization, or pseudoconditioning. Accordingly, experiments 2 and 3 were conducted to determine whether LSD's enhancement of conditioning could have arisen from its altering the sensory processing of either the CS or UCS, or both. In experiment 2, LSD was found to have no significant effect on the functions relating UCS magnitude to the frequency, amplitude, or number of sinusoidal peaks comprising each unconditioned response (UCR). In contrast, experiment 3 revealed that LSD significantly enhanced the frequency of CRs to an extended range of CS intensities and lowered the CS intensity threshold. It was concluded that the enhancing effect of LSD on the acquisition of CRs is attributable, at least in part, to the drug's enhancement of the sensory processing of the CS.

Sodium pentobarbital: sensory and associative effects in classical conditioning of the rabbit nictitating membrane response.

Four experiments were conducted to determine the effects of sodium pentobarbital (0, 3, 9, and 15 mg/kg) on the acquisition of the rabbit's classically conditioned nictitating membrane response (NMR) and to determine the locus of the drug's effects on sensory, motor, associative, and nonassociative processes. In experiment 1, classical conditioning of the NMR was accomplished by pairing tone and light conditioned stimuli (CSs) with paraorbital shock as the unconditioned stimulus (US). The experiment revealed that pentobarbital retarded the acquisition of conditioned responses (CRs) to both tone and light CSs. Experiment 2, employing unpaired CS, UCS presentations, indicated small but significant drug effects on NMR base rate and nonassociative NMRs to the CS. Experiment 3 revealed no significant drug effect on the psychophysical functions relating UCS intensity to UCR frequency or amplitude, nor on the UCS intensity threshold for eliciting UCRs. On the other hand, in experiment 4, the drug significantly impaired CR frequency over an extended range of CS intensities and raised CS intensity threshold. It was concluded that pentobarbital's attenuation of CS intensity also operated to impair CR acquisition.

Sensory and associative effects of morphine and naloxone in classical conditioning of the rabbit nictitating membrane response.

In Experiment I, classical conditioning of the rabbit's nictitating membrane response was accomplished by the pairing of tone and light conditioned stimuli with a shock unconditioned stimulus applied to the paraorbital region of the head. Morphine (5 mg/kg) significantly retarded the acquisition of conditioned responses to both conditioned stimuli. Moreover, morphine had no effect on nonassociative responding (baseline responding or responding to tone and light stimuli) or on the latency and amplitude of the unconditioned response elicited by shock during the explicitly unpaired presentations of tone, light and shock stimuli. The retardant effect of morphine on acquisition of conditioned responses was blocked by naloxone (1 mg/kg). In Experiment II, morphine (0.2-10 mg/kg) had no effect on the intensity threshold of the shock unconditioned stimulus for elicitation of unconditioned responses or on the latencies of the elicited responses. However, morphine (5 and 10 mg/kg) did produce a small but significant decrease in the amplitude of unconditioned responses elicited by the two highest shock intensities employed (3 and 4 mA). This latter effect of morphine was completely blocked by naloxone (1 mg/kg). In Experiment III, morphine (5 mg/kg) blocked the sensory processing of a tone conditioned stimulus, in previously trained animals, as measured by a significant (24 dB) elevation in the intensity threshold of the conditioned stimulus for elicitation of conditioned responses and an increase in the latency of the elicited response. Naloxone (1 mg/kg) completely blocked the effects of morphine on the sensory processing of the tone-conditioned stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Conditioning and reflex modification of the rabbit nictitating membrane response using electrical stimulation in auditory nuclei.

Electrical brain stimulation (EBS) was applied to four nuclei in the auditory system, namely, the cochlear nucleus (CN), superior olive (SO), inferior colliculus, and medial geniculate. EBS was also applied to the pontine nuclei, which are the main relays for transmitting auditory conditioned stimuli (CSs) into the cerebellar pathways for conditioning of the nictitating membrane response (NMR). EBS of the CN, but no other site, yielded reflex modification, which was an increase in the unconditioned NMR to an airpuff unconditioned stimulus (US) when preceded by EBS. Throughout the experiment, EBS of the SO produced a distinctive distribution of NMRs, in which a high proportion had latencies less than 50 ms. When EBS was repeatedly paired with the airpuff US, conditioned responses (CRs) were acquired to comparable levels across all sites. At each site, response likelihood was an increasing function of the EBS parameters of pulse amplitude, pulse frequency, and pulse width. Combined with anatomical findings, these results indicate that multiple encodings of an auditory CS are sent to the pathways for the NMR.

Localization of retractor bulbi motoneurons in the rabbit.

Motoneurons innervating the rabbit retractor bulbi muscle have been identified by retrograde transport of horseradish peroxidase (HRP). Following injection of HRP into single slips or all 4 slips of the retractor bulbi muscle, labeled motoneurons were consistently observed in the abducens (ABD) nucleus and in the accessory abducens (ACC) nucleus located ventral, lateral and rostral to the ABD. Axons from the ACC motoneurons could be seen to enter the VIth nerve. Injection of HRP into the lateral rectus muscle produced consistent labeling of motoneurons in the ABD nucleus overlapping the distribution of retractor bulbi motoneurons, but labeling was never observed in the ACC nucleus. The number of labeled ABD neurons after lateral rectus injections was far less (36%) than after injection into all 4 slips of the retractor bulbi muscle (72%). Injection of HRP into the superior oblique, superior rectus or medial rectus muscle produced labeling of motoneurons in the corresponding subdivisions of the oculomotor nucleus or trochlear nucleus but no labeled motoneurons were observed in either the ABD or ACC nuclei. Some highly inconsistent labeling of oculomotor nucleus was observed after retractor bulbi or lateral rectus muscle injections and this was judged to be due to intraorbital diffusion of the HRP. It was concluded that the retractor bulbi muscle is innervated by motoneurons located in both the ABD and ACC nuclei.

The role of the accessory abducens nucleus in the rabbit nictitating membrane response.

Electrolytic and knife-cut lesions were employed in the rabbit to examine the role of the VIth cranial nerve, and of the motoneurons in the abducens (ABD) and accessory abducens (ACC) nuclei that supply the VIth nerve, in the reflex extension of the nictitating membrane. The nictitating membrane response (NMR) was elicited by tactual stimulation of the cornea with a puff of air or by electric shock delivered to the skin over the paraorbital region of the head. Total destruction of the VIth nerve or interruption of all ACC inputs to the VIth nerve (while leaving ABD inputs intact) produced a large and comparable reduction in the magnitude of the NMR elicited by air puff, although a small residual NMR of less than 1 mm could still be detected. In contrast, the magnitude of the NMR elicited by shock was not affected by ACC isolation and only reduced by 50% after VIth nerve lesions. Total isolation of ABD inputs to the VIth nerve (while leaving ACC inputs intact) had no effect on NMR magnitude elicited by either air puff or shock. The small residual NMRs to air puff and the larger NMRs to shock remaining after total destruction of the VIth nerve were not eliminated by the removal of all extraocular muscles (while leaving the retractor bulbi muscle intact). However, knife cut lesions that interrupted all ACC inputs to the VIth nerve and transected the VIIth (facial) nerve completely eliminated NMRs elicited by both air puff and shock. The results of this study indicate that NMRs elicited by tactual stimulation of the cornea are primarily mediated by retractor bulbi motoneurons in the ACC nucleus via the VIth nerve. In contrast, NMRs elicited by electric shock delivered to the skin over the paraorbital region of the head are produced by contraction of the retractor bulbi muscle via the VIth nerve and by contraction of the orbicularis oculi muscle via the VIIth nerve which then squeezes the nictitating membrane over the cornea.

Conditioning of the rabbit's nictitating membrane response to a CSA-CSB-US serial compound: manipulations of CSB's associative character.

Response acquisition to a trace conditioned stimulus (CSA) can be facilitated by insertion of a second stimulus (CSB) at the end of the trace interval just before the unconditioned stimulus (US). This effect may arise from serial mediation of trace conditioning, second-order conditioning, or both. Whereas serial mediation relies only on the presence of CSB, associative transfer relies on CSB's associative strength. In the present experiments, the presence of CSB was fixed, whereas CSB's associative strength was manipulated by (a) extinction of CSB, (b) latent inhibition of CSB, and (c) prior CSB-US pairings. In the first 2 cases, the level of responding to CSA was reduced in a fashion parallel to that of CSB. However, in the third case, partial blocking of conditioned response (CR) acquisition to CSA was observed. The results are discussed with reference to the role of associative transfer to both facilitating and blocking CR acquisition to CSA.

Differential conditioning of the rabbit's nictitating membrane response to serial compound stimuli.

Three experiments were conducted to determine the time course and contents of CS representations through an examination of differential conditioning of the rabbit's nictitating membrane response to two serial compounds. One compound (A-X+) was always paired with the unconditioned stimulus, and the other (B-X-) was always presented alone. All three experiments entailed manipulation of the interstimulus interval between the initial distinctive element of each compound (A and B) and the second, shared element (X). The joint results revealed that (a) conditioned response acquisition to the initial elements depended on the presence of X in the A-X+ compound; (b) differentiation between A and B appeared across interstimulus intervals up to 4,600 ms; and (c) conditional control over responding following A and B appeared at interstimulus intervals of at least 4,600 ms and perhaps up to 12,600 ms. The results are discussed with respect to mechanisms of occasion setting, generalization, and configuration.

Associative transfer and stimulus selection in classical conditioning of the rabbit's nictitating membrane response to serial compound CSs.

Four experiments were conducted to determine whether in conditioning to a serial compound, CS1-CS2-UCS, there are (a) associative mechanisms operating to extend conditioning beyond the bounds of a CS-UCS contiguity gradient and (b) stimulus selection processes acting to attenuate the potency of CS-UCS contiguity. In Experiments 1 and 2, the CS2-UCS interval was held at .35 sec while the CS1-UCS interval was varied across groups from .75 to 2.75 sec. CS1 test trials revealed substantial CR acquisition at all CS1-UCS intervals. Moreover, Experiment 2 indicated that when the contribution of cross-modal generalization from CS2 to CS1 was factored out, there still remained a substantial level of conditioning, which Experiment 3 indicated was attributable to an associative mechanism like higher-order or sensory conditioning. The observation of CR acquisition at CS1-UCS intervals of 4.75, 8.75, and 18.75 sec in Experiment 4 suggested that serial compound training yields conditioning to CSs located well beyond the single CS contiguity gradient for the rabbit's nictitating membrane response. Experiments 1 and 2 also indicated the presence of stimulus selection processes because, at the shorter CS1-UCS intervals (.75 and 1.25 sec), the levels of test-trial responding to CS2 fell below those observed to the less contiguous CS1.

MDA effects on classical appetitive conditioning of the rabbit jaw movement response.

We determined MDA's effects on: (a) conditioning of the rabbit's jaw movement response (JMR) (Experiment 1); and (b) nonassociative JMRs and unconditioned JMRs (Experiment 2). Rabbits were administered 3,4-methylenedioxyamphetamine (MDA; 0, 2, or 4 mg/kg) into the marginal ear vein 20-30 min prior to each of 10 daily sessions. Experiment 1 involved 30 daily training trials of 15 tone- and 15 light-conditioned stimuli (CSs) paired with a 1-ml squirt of water, as the unconditioned stimulus (UCS), injected into the oral cavity. The study revealed that MDA impaired conditioned response (CR) acquisition to tone-CS trials while augmenting CRs to light-CSs. In Experiment 2, the animals received 15 tone- and 15 light CS-alone and 30 UCS-alone presentations daily. The study revealed that MDA produced a modest increase in nonassociative responses over days that interacted with CS modality. Accordingly, these nonassociative effects could not account for MDA's influences on CR acquisition. Moreover, MDA's decrementing and enhancing of CRs to tone- and light-CSs, respectively, appears to be attributable to the drug's enhancing or decrementing tone- and light-CS intensity.

Effects of cocaine on conditioning of the rabbit nictitating membrane response.

Two experiments were conducted to determine cocaine's (0, 1, 3, and 6 mg/kg) effects on associative, nonassociative, and motor processes in classical conditioning of the rabbit's nictitating membrane response (NMR). In Experiment 1, acquisition training consisted of tone- and light-conditioned stimuli (CSs) each paired on separate trials with a shock unconditioned stimulus (UCS). Cocaine injected prior to each session significantly impaired acquisition of conditioned responses (CRs). In Experiment 2, rabbits received cocaine injections prior to each training session involving explicitly unpaired CS-alone and UCS-alone presentations. Cocaine had no significant effects upon: base rate of NMRs; frequency of NMRs during presentations of the CSs; and frequency, amplitude, and latency of the UCRs. Consequently, cocaine's impairment of CR acquisition could not be attributed to its effects upon the nonassociative processes of base rate, sensitization, and pseudoconditioning, nor upon the sensory processing of the UCS and/or motor functioning of the UCR. Rather, cocaine's effects upon CR acquisition were mediated by the drug's effect upon associative processes. It appears likely that the drug affected the ability of the CS to enter into the associative conditioning process.

Effects of MDA on classical conditioning of the rabbit nictitating membrane response.

In Experiment 1, classical conditioning of the rabbit's nictitating membrane response (NMR) was accomplished by pairing tone and light conditioned stimuli (CSs) with a shock unconditioned stimulus (UCS). MDA impaired the acquisition of conditioned responses (CR) to a tone-CS, while significantly enhancing CR acquisition to a light-CS. Experiment 2, employing explicitly unpaired CS, UCS training, revealed no reliable effects of MDA upon nonassociative processes. Subsequent efforts determined if MDA's CR acquisition effects resulted from alterations in sensory processing of the CS, UCS, and/or UCR motor functioning. Specifically, it was determined that MDA: (a) increased the tone-CS intensity threshold for eliciting CRs (Experiment 3); (b) attenuated the tone-induced reflex modification of the unconditioned NMR (Experiment 4); and (c) enhanced UCR frequency at varying UCS intensities (Experiment 5). It was concluded that MDA's effect upon CR acquisition reflected the drug's effect upon CS and UCS/UCR processing and thereby altered the ability of these components of conditioning to enter into associative learning.

Nitrous oxide: sensory, motor, associative, and behavioral tolerance effects in classical conditioning of the rabbit nictitating membrane response.

Experiment 1, of a series of six experiments with the rabbit nictitating membrane response (NMR) preparation, revealed that nitrous oxide (0%, 33%, 67%) impaired acquisition of conditioned responses (CRs). Subsequent experiments indicated that nitrous oxide (N2O) had no reliable effects upon nonassociative processes (Experiment 2); impaired unconditioned response (UR) amplitude (Experiment 3); attenuated tone-conditioned stimulus (CS) intensity (Experiment 4); decremented tone-induced reflex modification of the unconditioned NMR (Experiment 5); and demonstrated no reliable evidence of behavioral tolerance (Experiment 6). It was concluded that N2O's impairment of CR acquisition was attributable to its attenuation of the intensity of tone CSs and shock USs and/or UR amplitude. These findings are consistent with the behavioral laws of conditioning: the attenuation of the intensive sensory properties of the CS and US and/or UR components of conditioning affect their ability to enter into the establishment of CS-CR connections and, therefore, the development of associative learning.

Effect of LSD on acquisition, maintenance, extinction and differentiation of conditioned responses.

Three experiments were conducted to compare the effects of LSD (30 nmol/kg) on the acquisition, maintenance, extinction and differentiation of the rabbit's classically conditioned nictitating membrane response. LSD significantly enhanced the acquisition of conditioned responses to tone and light conditioned stimuli as compared with vehicle injected controls (Experiments 1 and 2), but had no detectable effect on differential conditioning in Experiment 3. The conditioned responses acquired under LSD in Experiments 1 and 2 exhibited some unusual features in that: they were more rapidly extinguished under continued injections of LSD; they demonstrated a significant decrement when animals were switched from LSD to vehicle during maintenance; and they were virtually eliminated when animals were switched from LSD to vehicle during extinction. In contrast, conditioned responses acquired under saline injections in Experiments 1 and 2 were not affected when animals were switched to LSD injections during either maintenance or extinction. These results of Experiments 1 and 2 were interpreted as indicating that LSD produces an asymmetrical state-dependent learning.

Effects of morphine and LSD on the classically conditioned nictitating membrane response.

Two experiments were carried out to determine the effects of LSD and morphine on the unconditioned nictitating membrane response of the rabbit elicited by 5 intensities of a 100 msec puff of air directed at the cornea, and on the acquisition of conditioned responses to a tone and light conditioned stimulus using the air-puff as an unconditioned stimulus. In Experiment 1, LSD tartrate (0.013 mg/kg) had no effect of the frequency, amplitude, magnitude or latency of the unconditioned response. However, LSD significantly enhanced the rate of acquisition of conditioned responses to both tone and light conditioned stimuli. In Experiment 2, morphine sulfate (5 mg/kg) had no effect on the frequency, amplitude, magnitude or latency of the unconditioned response, but significantly retarded the acquisition of conditioned responses to both tone and light conditioned stimuli. The results indicated that the enhancement of acquisition produced by LSD and the retardation of acquisition produced by morphine were not due to effects of the drugs on either the sensory processing of the air-puff unconditioned stimulus or on the motoric expression of the unconditioned response.