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G F Koob

Publications and source records attributed to G F Koob.

At least 361 records · Page 20Linked to original sources
PubMed1983

Paradoxical reinforcing properties of apomorphine: effects of nucleus accumbens and area postrema lesions.

Apomorphine (0.01-10.0 mg/kg, subcutaneously) paradoxically produced both dose-dependent aversive and positive reinforcing effects, as measured in conditioned taste aversion and place preference paradigms, respectively. The conditioned taste aversions produced by apomorphine were not modified in rats with bilateral 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens (producing 92% depletion of dopamine in the nucleus accumbens) nor in rats with thermal lesions of the area postrema. Both types of lesions were behaviorally verified as effective in other paradigms; the 6-OHDA lesions potentiated the facilitatory effects to a novel flavor paired with scopolamine methylnitrate (1.0 mg/kg, intraperitoneally). However, 6-OHDA lesions of the nucleus accumbens did clearly potentiate the conditioned place preferences induced by apomorphine. These results suggest that both the positive reinforcing and locomotor effects of apomorphine may partially result from activation of post-synaptic dopamine receptors in the nucleus accumbens. Moreover, the dissociation of apomorphine's aversive and positive reinforcing properties revealed by the 6-OHDA lesions may provide the first step in attempts to pinpoint the different brain sites of action where apomorphine produces its opposite motivational effects.

Animals↗
PubMed1983

Vasopressin potentiation in the performance of a learned appetitive task: reversal by a pressor antagonist analog of vasopressin.

Rats were tested in a simple one-trial water-finding task for the effects of arginine vasopressin (AVP) on performance of an appetitive task. On the training day, each animal was exposed for 5 min to a novel open-field environment that contained a water-tube located in an alcove set into one of the walls of the enclosure. Immediately upon removal from the enclosure, the animals received a subcutaneous injection of either AVP (1 microgram/rat) or vehicle solution. When water-deprived and tested 48 hr later, vasopressin-treated rats found the water tube reliably faster than controls. In other groups of animals, this potentiation in learned performance was prevented by concurrently treating the rats with a vasopressin analog having potent pressor antagonist properties. These results are consistent with the notion that vasopressin may play a role in memory consolidation, but peripheral visceral factors may mediate this action.

Animals↗
PubMed1983

Can aversive properties of (peripherally-injected) vasopressin account for its putative role in memory?

Rats injected with arginine vasopressin (AVP) immediately after exposure to a novel open-field environment found a water tube faster than saline injected rats, when water-deprived 48 h later. Other experiments demonstrated that this effect did not result from some conditioned or pharmacologically-induced hyperactivity in the experimental group. Although these results are consistent with a role for AVP in 'memory' mechanisms, lithium chloride, a known illness-producing agent, produced a reduction in latency to find the water tube identical to that of AVP. In separate experiments, AVP acted as an effective unconditioned stimulus in conditioned taste and place aversion studies. AVP also produced a dose-dependent disruption of spontaneous locomotor activity. Together, these data indicate that peripheral AVP administration has aversive consequences. Desglycinamide arginine vasopressin (an AVP analog with weak pressor-agonist properties) produced no observable aversive effects and did not improve test performance in the appetitive water-finding task. It is suggested that the apparent memory-enhancing properties of peripherally administered AVP, at least in appetitive test paradigms, may depend on its aversive and consequently arousing actions.

Animals↗
PubMed1983

The effect of single and repeated electroconvulsive shock (ECS) on locomotor activity in rats.

Locomotor activity following administration of apomorphine (0.1 mg/kg), and amphetamine (1 mg/kg) was studied in rats receiving single and multiple electroconvulsive shock (ECS). Three groups of rats were utilized, one half of each group received sham treatment and the other half received either 1,5, or 10 daily ECS. Significant enhancement of the locomotor response to amphetamine, but not apomorphine, was seen in rats given repeated ECS as compared to controls. This study suggests that the number of ECS, is an important variable in ECS enhancement of locomotor response to amphetamine.

Animals↗
PubMed1983

Effects of d-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens.

After training under a fixed-interval 60 sec schedule of food presentation in the presence of a water tube (to permit schedule-induced licking), groups of rats received either 6-hydroxy-dopamine (6-OHDA)(8 micrograms base/2 microliters) or 0.2% ascorbate-0.9% saline vehicle bilaterally into the nucleus accumbens. 6-OHDA produced greater than 80% depletion of the catecholamines dopamine and norepinephrine and the dopamine metabolite dihydroxyphenylacetic acid in the nucleus accumbens and olfactory tubercle, but nonsignificant depletions in the corpus striatum. The behavior of the groups treated with 6-OHDA ("lesion") and vehicle ("sham") was assessed for up to 58 days postoperatively. In the first few days after 6-OHDA, the lesion group showed reductions in high rates of responding toward the end and in high rates of licking at the beginning of the fixed-interval. However, licking was increased during later portions of the fixed interval in the lesion group. d-Amphetamine (0.25-2.0 mg/kg) increased low rates but decreased high rates of schedule-controlled responding, while generally reducing licking. The lesion group showed attenuated rate-reducing effects of d-amphetamine. In contrast, the lesion group showed enhanced rate-reducing effects of apomorphine (0.025-0.1 mg/kg) on both schedule-controlled responding and schedule-induced licking. In a second determination of the effect of d-amphetamine (0.25-2.0 mg/kg), schedule-induced locomotor activity was recorded and the water tube was removed. The lesion group showed attenuated rate-increasing and rate-decreasing effects of d-amphetamine upon schedule-controlled responding and reductions in the drug-induced increases in locomotor activity. The results are discussed in terms of the functions of dopamine in the control of behavior and in the mediation of the response to d-amphetamine and apomorphine.

Animals↗
PubMed1982

Intraventricular corticotropin-releasing factor enhances behavioral effects of novelty.

Corticotropin-releasing factor was administered into the lateral cerebral ventricles of rats. Sixty minutes later, animals were tested in an open field conflict test or in their home cages for a variety of behaviors which have been shown to be related to the degree of responsiveness to novelty. CRF, in a dose related fashion, altered the frequency of those behaviors which are normally expressed in response to the novel environment. Specifically, CRF caused an increase in grooming and decreases in the amount of rearing, the number of approaches to a food pellet placed in the center of the open field, the amount of food eaten in both the open field and the home cage and a decrease in the mean amount of food eaten per approach to the food pedestal.

Animals↗
PubMed1982

Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems.

The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press of IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine self-administration. Similarly, pretreatment with low doses of the dopamine antagonist drug alpha-flupenthixol produced dose-dependent increases in cocaine but not heroin self-administration. High doses of alpha-flupenthixol eliminated all responding for cocaine and slightly reduced heroin self-administration. The specificity with which the two antagonist drugs exerted their behavioral effects strongly suggests that independent neural substrates are responsible for the reinforcing actions of heroin and cocaine.

Animals↗
PubMed1982

Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats.

6-Hydroxydopamine-induced destruction of dopaminergic terminals in the nucleus accumbens have been shown previously to disrupt cocaine and amphetamine self-administration. We sought to determine whether lesions of the DA cell bodies in the ventral tegmental area (VTA) which give rise to the DA innervation of the n. accumbens, would also disrupt cocaine self-administration behavior. Rats were trained to self-inject cocaine (0.75 mg/kg) for 4 hr/day. After a stable baseline was established, one group of rats received bilateral injections of 6-OHDA (4 micrograms/l microliter) into the VTA. Control rats received vehicle injections. When retested on the fifth day post-lesion, all of the 6-OHDA treated animals showed a long lasting reduction in cocaine intake. Three animals did not reinitiate cocaine self-administration after the lesion, although each showed stable post-lesion responding for apomorphine. The surgery had no effect on cocaine self-administration in control animals. These data support the hypothesis that dopaminergic mechanisms are necessary for the normal expression of cocaine self-administration.

Animals↗
PubMed1982

Apomorphine-induced facilitation of intracranial self-stimulation following dopamine denervation of the nucleus accumbens.

Two groups of rats were trained to lever press for intracranial self-stimulation (ICSS) from electrodes aimed at the posterior lateral hypothalamus or at the region of the locus coeruleus. Following stabilization of baseline responding using descending rate/intensity functions, bilateral 6-hydroxydopamine (6-OHDA) lesions to the nucleus accumbens (N.Acc.) were performed. Subsequent injections of apomorphine (SC) resulted in significant increases in self-stimulation in both lesion groups and significant decreases in self-stimulation in both groups of sham operated animals. These results indicate that the destruction of the dopaminergic terminals in the nucleus accumbens results in a "supersensitive" enhancement of the ICSS stimulating properties of apomorphine regardless of the electrode placement. Both lesion groups also showed a pronounced increase in locomotor activity in photocell cages following treatment with the same dose of apomorphine. These results complement previous work showing that dopamine destruction affects ICSS regardless of electrode placement and support the hypothesis that the midbrain dopamine systems have a general response enabling role in reinforced behavior.

Animals↗
PubMed1982

Changes in locomotor response to beta-endorphin microinfusion during and after opiate abstinence syndrome--a proposal for a model of the onset of mania.

Beta-Endorphin (0.3 or 0.6 nanomoles) was infused into the A10-ventral tegmental area (VTA) of male Wistar rats previously treated for 6 days with either morphine sulfate or lactose via subcutaneously implanted silastic pellets. Beta-Endorphin microinfusions occurred at 24 and 96 hours after pellets were removed. Profound changes in locomotor response to beta-endorphin were found, with morphine-pretreated rats showing a spontaneous switch from hyporesponsiveness to hyperresponsiveness over 72 hours, compared to lactose-pretreated controls. These findings may reflect on current biochemical theories regarding the "switch" process in bipolar affective disease. The data can be viewed within a heuristic model of receptor changes which may underlie the transition from depression to mania.

Affective Disorders, Psychotic↗
PubMed1981

The behavioural effects of enkephalin analogues injected into the ventral tegmental area and globus pallidus.

Two stable analogues of enkephalin D-Ala2-Met5-enkephalinamide (DAMA) and D-Ala2,D-Leu5-enkephalin (DADLE) injected bilaterally into the ventral tegmental area (VTA) induced locomotion, characterized by bursts of morphine-like activity. The response of DADLE was blocked by systemic-alpha-flupenthixol (0.2 mg/kg) and naloxone (1 mg/kg). At higher doses of enkephalins in the VTA, stereotypy behaviour involving gnawing, became apparent. When injected bilaterally into the globus pallidus (GP), both analogues induced a dose-dependent increase in locomotor activity but stereotypy was not observed. The locomotor behaviour induced by DADLE was blocked by naloxone but not by alpha-flupenthixol. These results suggest that naloxone-sensitive opiate receptors modulate, at a number of different sites, the neural pathways involved in the expression of behavioural activity.

Animals↗