A pinboard by
Geith Maal-Bared

I'm interested in journalism. I find myself drawn to the challenge of communicating science with unwatered-down accuracy. I'm an avid consumer (and writer, I suppose) of music; I'm fascinated by the ever-changing nature of popular music and the factors that contribute to the emergence of musical subcultures and movements. I enjoy baking and the indescribable sensory experience of cinnamon buns.


This pinboard contains articles that support the deprived/non-deprived theory of motivation.

The deprived/non-deprived theory of motivation asserts that the neural underpinnings of food- and drug-elicited reinforcement vary based on the subject's prior exposure to the substance. Specifically, dopaminergic pathways are not necessary for drug and food reinforcement unless the subject is in a state of deprivation. On the other hand, the tegmental pedunculopontine nucleus (TPP) of the brainstem is necessary for reinforcement in non-deprived (or drug-naive) animals. This double dissociation has been demonstrated with many substances (e.g., food, nicotine, ethanol, opiates etc). Drug dependence can be thought of as a phenomenon whereby the abused substance no longer induces pleasure and becomes merely a means to alleviate withdrawal. The papers pinned herein provide a more in-depth look on the molecular mechanisms that alter one's motivation to seek reinforcing stimuli.


The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the alpha7-subunit-containing nicotinic acetylcholine receptor.

Abstract: Within the mammalian ventral tegmental area (VTA), nicotine produces both aversive and rewarding motivational effects. However, the specific neuronal nicotinic acetylcholine receptor (nAChR) subtypes responsible for these effects are not clearly understood.In the present study, we challenged the motivational effects of nicotine directly in the VTA with nAChR subunit specific antagonists.Using an unbiased place-conditioning procedure as a behavioural assay, we performed bilateral microinfusions of nicotine over a wide range of concentrations (0.008, 8, 24 and 48 nmol/0.5 microl) and challenged the aversive and reinforcing behavioural effects of these nicotine doses with co-administration of di-hydro-beta-erythroidine (DHbetaE) (5 or 50 nmol/0.5 microl), a nAChR antagonist with higher relative affinity for the alpha4beta2 nAChR subunit, methyllycaconitine citrate (MLA) (0.4 or 4 nmol/0.5 microl), a nAChR antagonist that displays greater relative affinity for the alpha7 nAChR, and the NMDA receptor antagonist, d-2-amino-7-phosphoheptanoic acid (AP-7; 18 nmol/0.5 microl).The alpha4beta2 antagonist DHbetaE blocked both the rewarding and aversive properties of intra-VTA nicotine. However, the alpha7 antagonist MLA blocked nicotine reward and switched the motivational valence of higher doses of nicotine (8-48 nmol/0.5 microl) from rewarding to aversive. The NMDA antagonist AP-7 blocked both the aversive and rewarding effects of intra-VTA nicotine.These results suggest a functional dissociation between nAChR neural substrates within the VTA that mediate the bivalent motivational properties of nicotine and further suggest that nicotine may produce its motivational effects through a glutamatergic mechanism.

Pub.: 06 Feb '03, Pinned: 31 Aug '17

A test of the opponent-process theory of motivation using lesions that selectively block morphine reward.

Abstract: The opponent-process theory of motivation postulates that motivational stimuli activate a rewarding process that is followed by an opposed aversive process in a homeostatic control mechanism. Thus, an acute injection of morphine in nondependent animals should evoke an acute rewarding response, followed by a later aversive response. Indeed, the tegmental pedunculopontine nucleus (TPP) mediates the rewarding effects of opiates in previously morphine-naive animals, but not other unconditioned effects of opiates, or learning ability. The aversive opponent process for acute morphine reward was revealed using a place-conditioning paradigm. The conditioned place aversion induced by 16-h spontaneous morphine withdrawal from an acute morphine injection in nondependent rats was abolished by TPP lesions performed prior to drug experience. However, TPP-lesioned rats did show conditioned aversions for an environment paired with the acute administration of the opioid antagonist naloxone, which blocks endogenous opioids. The results show that blocking the rewarding effects of morphine with TPP lesions also blocked the opponent aversive effects of acute morphine withdrawal in nondependent animals. Thus, this spontaneous withdrawal aversion (the opponent process) is induced by the acute rewarding effects of morphine and not by other unconditioned effects of morphine, the pharmacological effects of morphine or endogenous opioids being displaced from opiate receptors.

Pub.: 06 Jul '07, Pinned: 31 Aug '17

Different neural systems mediate morphine reward and its spontaneous withdrawal aversion.

Abstract: The opponent-process theory posits that the aversive state of acute opiate withdrawal is a consequence of, and depends on, the previous rewarding state evoked by acute morphine reward. Although the brainstem tegmental pedunculopontine nucleus (TPP) is crucial for the rewarding component of morphine, the source of the later aversive component is not known. It is possible that (i) the second aversive process takes place within the TPP itself or (ii) morphine reward in the TPP activates an unconditioned opponent motivational process in another region of the brain. The effects of reversible inactivation of the TPP on the motivational properties of acute morphine and its spontaneous withdrawal effects in non-drug-dependent rats were examined using a place-conditioning paradigm. Reversible inactivation of the TPP with lidocaine or bupivacaine immediately before the morphine injection blocked the rewarding properties of morphine in non-dependent rats. Blocking the rewarding effects of morphine also blocked the opponent aversive effects of acute morphine withdrawal. In contrast, reversible inactivation of the TPP during the acute morphine withdrawal did not block this opponent aversive process. Our results confirm that the TPP is a critical neural substrate underlying the acute rewarding effects of morphine in non-dependent rats. Furthermore, the opponent aversive process of acute morphine withdrawal is induced by the acute rewarding effects of morphine. However, the TPP does not directly mediate the spontaneous withdrawal aversion (the opponent process), suggesting that a different system, triggered by the changes in the TPP after the primary drug response, produces the aversion itself.

Pub.: 21 May '09, Pinned: 31 Aug '17

Adenosine A1 and A2A receptors are not upstream of caffeine's dopamine D2 receptor-dependent aversive effects and dopamine-independent rewarding effects.

Abstract: Caffeine is widely consumed throughout the world, but little is known about the mechanisms underlying its rewarding and aversive properties. We show that pharmacological antagonism of dopamine not only blocks conditioned place aversion to caffeine, but also reveals dopamine blockade-induced conditioned place preferences. These aversive effects are mediated by the dopamine D(2) receptor, as knockout mice showed conditioned place preferences in response to doses of caffeine that C57Bl/6 mice found aversive. Furthermore, these aversive responses appear to be centrally mediated, as a quaternary analog of caffeine failed to produce conditioned place aversion. Although the adenosine A(2A) receptor is important for caffeine's physiological effects, this receptor seems only to modulate the appetitive and aversive effects of caffeine. A(2A) receptor knockout mice showed stronger dopamine-dependent aversive responses to caffeine than did C57Bl/6 mice, which partially obscured the dopamine-independent and A(2A) receptor-independent preferences. Additionally, the A(1) receptor, alone or in combination with the A(2A) receptor, does not seem to be important for caffeine's rewarding or aversive effects. Finally, excitotoxic lesions of the tegmental pedunculopontine nucleus revealed that this brain region is not involved in dopamine blockade-induced caffeine reward. These data provide surprising new information on the mechanism of action of caffeine, indicating that adenosine receptors do not mediate caffeine's appetitive and aversive effects. We show that caffeine has an atypical reward mechanism, independent of the dopaminergic system and the tegmental pedunculopontine nucleus, and provide additional evidence in support of a role for the dopaminergic system in aversive learning.

Pub.: 26 Jun '10, Pinned: 31 Aug '17

Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal.

Abstract: Nicotine, the main psychoactive ingredient of tobacco smoke, induces negative motivational symptoms during withdrawal that contribute to relapse in dependent individuals. The neurobiological mechanisms underlying how the brain signals nicotine withdrawal remain poorly understood. Using electrophysiological, genetic, pharmacological, and behavioral methods, we demonstrate that tonic but not phasic activity is reduced during nicotine withdrawal in ventral tegmental area dopamine (DA) neurons, and that this pattern of signaling acts through DA D2 and adenosine A2A, but not DA D1, receptors. Selective blockade of phasic DA activity prevents the expression of conditioned place aversions to a single injection of nicotine in nondependent mice, but not to withdrawal from chronic nicotine in dependent mice, suggesting a shift from phasic to tonic dopaminergic mediation of the conditioned motivational response in nicotine dependent and withdrawn animals. Either increasing or decreasing activity at D2 or A2A receptors prevents the aversive motivational response to withdrawal from chronic nicotine, but not to acute nicotine. Modification of D1 receptor activity prevents the aversive response to acute nicotine, but not to nicotine withdrawal. This double dissociation demonstrates that the specific pattern of tonic DA activity at D2 receptors is a key mechanism in signaling the motivational effects experienced during nicotine withdrawal, and may represent a unique target for therapeutic treatments for nicotine addiction.

Pub.: 07 Feb '12, Pinned: 31 Aug '17

Ventral tegmental area GABA neurons and opiate motivation.

Abstract: Past research has demonstrated that when an animal changes from a previously drug-naive to an opiate-dependent and withdrawn state, morphine's motivational effects are switched from a tegmental pedunculopontine nucleus (TPP)-dependent to a dopamine-dependent pathway. Interestingly, a corresponding change is observed in ventral tegmental area (VTA) GABAA receptors, which change from mediating hyperpolarization of VTA GABA neurons to mediating depolarization.The present study investigated whether pharmacological manipulation of VTA GABAA receptor activity could directly influence the mechanisms underlying opiate motivation.Using an unbiased place conditioning procedure, we demonstrated that in Wistar rats, intra-VTA administration of furosemide, a Cl(-) cotransporter inhibitor, was able to promote a switch in the mechanisms underlying morphine's motivational properties, one which is normally observed only after chronic opiate exposure. This behavioral switch was prevented by intra-VTA administration of acetazolamide, an inhibitor of the bicarbonate ion-producing carbonic anhydrase enzyme. Electrophysiological recordings of mouse VTA showed that furosemide reduced the sensitivity of VTA GABA neurons to inhibition by the GABAA receptor agonist muscimol, instead increasing the firing rate of a significant subset of these GABA neurons.Our results suggest that the carbonic anhydrase enzyme may constitute part of a common VTA GABA neuron-based biological pathway responsible for controlling the mechanisms underlying opiate motivation, supporting the hypothesis that VTA GABAA receptor hyperpolarization or depolarization is responsible for selecting TPP- or dopamine-dependent motivational outputs, respectively.

Pub.: 09 Feb '13, Pinned: 31 Aug '17