No abstract

The feeding-relevant pathway by which food restriction (FR) augments cocaine action is unknown. Systemic administration of the 28-amino acid acylated peptide ghrelin (1−10 nMol) increases food intake in rats and circulating levels of rat ghrelin are up-regulated by FR. The present experiment examined the impact of repeated administration of ghrelin or vehicle on the subsequent capacity of cocaine to enhance locomotion in rats. Male Sprague-Dawley rats were pretreated daily for seven days with 0, 5 or 10 nMol rat ghrelin (i.p.) in the home cage. On the 8 th day, rats were transported to a testing room, placed in a locomotion chamber for 15 min, and then injected (i.p.) with 0, 7.5, or 15 mg/kg cocaine hydrochloride. Locomotor activity was monitored over a 45 min post-cocaine period. Pretreatment with 5 or 10 nMol ghrelin alone did not significantly increase basal locomotion relative to that of the 0 nMol ghrelin group. Rats pretreated with 5 nMol or 10 nMol ghrelin showed an enhanced locomotor response after treatment with 15 mg/kg cocaine relative to rats treated with 0 nMol ghrelin. These results indicate that acute injection of ghrelin, at a feeding-relevant dose, can augment the acute effects of cocaine on locomotion in rats. KeywordsFood deprivation; Locomotion; Growth Hormone Food restriction (FR) is known to augment the locomotor actions of psychostimulant drugs such as cocaine or amphetamine (Bell et al., 1997;Campbell and Carroll, 2001;Carr, 2002;Carroll and Meisch, 1980, 1981). Additionally, FR acts to facilitate the acquisition of cocaine or amphetamine self-administration (Carroll, 1985) and augments the acquisition of cocaineinduced conditioned place preference (Bell et al., 1997). When animals already trained to selfadminister cocaine are deprived of food, their daily drug intake increases and FR can facilitate the reinstatement of cocaine-seeking behavior (Carroll, 1985). Conversely, food satiation can delay the acquisition of cocaine self-administration (Carroll and Lac, 1998). These findings suggest that feeding and drug addiction may share common pathways (DiLeone et al., 2003).The neural substrate through which the hyperlocomotor and reinforcing actions of drugs such as cocaine or amphetamine are enhanced by FR remains unknown (Carr, 2002). The stomach peptide ghrelin is an endogenous ligand for the growth-hormone secretagogue receptor (Kojima et al., 1999;Tschop et al., 2000) and functions as an orexigen receptor (Ariyasu et al. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Inui et al., 2004;Naleid et al., 2005;Wren et al., 2001a;Wren et al.,...

Serum total creatine kinase (CK) and the lactate dehydrogenase (LDH) isoenzymes were studied in 38 sedentary middle-aged men (aged 35-50 yrs) during a 30 week marathon training programme. Basal CK activity rose by 33% after 15 weeks but a significant rise (27%) in LDH activity took 30 weeks to occur. Post-exercise (maximum test on a bicycle ergometer) CK and LDH activities were higher than pre-exercise levels but the increment in enzyme activity following exercise did not change. LDH1 and LDH2 isoenzyme activity increased by 2.5% and 4% of total LDH respectively while LDH3 and LDH5 decreased by 3.9% and 2.4% respectively over 30 weeks. Post marathon total CK did not correlate with finishing time at 30 mins or 30 hrs post race. The range of CK MB isoenzyme activity at 30 mins post race was 1.8-9.8% of total CK with 11 subjects having a value above 6%. The training programme appears not to have affected muscle CK and LDH release during exercise but isoenzyme distribution changes reflect the adaptations known to occur in muscle during endurance training. Unfortunately only 16 subjects were available for all the investigations, and it is these upon whom most of the data were obtained.

The alkaloid lobeline inhibits the function of vesicular monoamine and dopamine transporters and diminishes the behavioral and neurochemical effects of nicotine and amphetamines. In the present study, we examined the interaction of systemic administration of lobeline on breakpoint scores on a progressive ratio (PR) schedule of intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB). Rats were run in two 30 min sessions, separated by a 10 min timeout period. At the end of the first session, each rat was injected with either 0, 0.5, 1.0 or 2.0 mg/kg (i.p.) lobeline. Positive controls known to suppress and to augment ICSS responding included the adrenergic antagonist prazosin (0, 0.5 and 2.0 mg/kg, i.p.) and the psychostimulant cocaine (0, 1.25, and 5.0 mg/kg, i.p.). Analyses of changes in average PR breakpoint scores between the 2 sessions revealed that lobeline significantly suppressed PR scores at doses of 0.5, 1.0 and 2.0 mg/kg, as did 0.5 mg/kg and 2.0 mg/ kg prazosin. These changes are unlikely to reflect motoric effects of these drugs inasmuch as neither lobeline nor prazosin alter locomotion at these doses. In contrast, PR breakpoint scores were significantly increased at 5.0 mg/kg cocaine, a dose that is sufficient to elevate locomotion in the rat. These results are consistent with the view that lobeline modulates brain reinforcement processes. Keywords Nicotinic receptors; Prazosin; CocaineMultiple behavioral assays can be used to index abuse potential [1][2][3] including the capacity of a drug to induce hyperlocomotion [4] and the capacity to induce conditioned place preference [5]. Rats will self-administer drugs such as cocaine or amphetamine into their vascular system [6]. Such drug infusions are thought to act on the neural substrates of reward. Electrodes placed along the path of the medial forebrain bundle (MFB) will support intracranial self-stimulation (ICSS) [7] and drugs of abuse are known to reduce the threshold current required to support ICSS [4,8,9]. Additionally, drugs of abuse are known to elevate progressive ratio (PR) responding for ICSS [10,11]. The latter types of studies are important in that a PR schedule, relative to a continuous reinforcement schedule, may be more sensitive to changes in reward engendered by neurotransmitter receptor antagonism [12].The alkaloid lobeline is derived from lobelia inflata [13]. Lobeline attenuates the hyperactivity induced by methamphetamine in rats and diminishes methamphetamine self-administration in rats [14][15][16]. The aforementioned results suggest that lobeline may function as a therapeutic tool for the treatment of methamphetamine abuse. Inasmuch as the impact of lobeline on ICSS responding has not been previously reported, the present study considered the impact of lobeline on breakpoints on a PR schedule of ICSS reinforcement. In this paradigm, the response requirement for reinforcement is increased systematically within a 30 min session [17]. Following completion of the first session, each rat was injected (i.p.)...

Psychostimulants including amphetamine and cocaine induce locomotion and stereotypy and suppress eating. Although the capacity of cocaine to alter locomotion is usually viewed as related to dopamine neurotransmission, recent studies suggest that norepinephrine, acting through alpha1-adrenergic receptors (alpha1-ARs) can facilitate cocaine-stimulated locomotion. Of the three alpha1-AR subtypes (alpha(1A), alpha(1B), and alpha(1D)) identified to date, inactivation of the alpha(1B)-AR subtype diminishes cocaine-stimulated locomotion, whereas the impact of inactivation of the alpha(1A)-AR subtype on either eating or locomotion is unknown. In the present study, we assessed the relative impact of ICV administration of the alpha(1B)-AR antagonist 5-methylurapidil (5-MU) on cocaine-stimulated hyperlocomotion and hypophagia, using a concurrent method [Wellman, P.J., Ho, D.H., Davis, K.W., 2005. Concurrent measures of feeding and locomotion in rats. Physiology of Behavior 84 (5), 769-774.]. Rats were infused ICV with one of 3 doses of 5-MU (0, 3, or 30 nmol) and then injected (i.p.) with 0, 2.5, 5.0, 10.0, or 20.0 mg/kg cocaine HCl on each of five tests. Rats always received the same 5-MU dose, but a different cocaine dose on each trial. Feeding and locomotion were assessed concurrently during a 45-min postinjection period. Significant suppression of eating was noted at 2.5 mg/kg cocaine, a dose that does not alter forward locomotion in the rat. Administration of 5-MU did not alter locomotion in rats treated with saline, but did significantly increase baseline food intake. Neither cocaine-induced hypophagia nor hyperlocomotion was altered by ICV administration of 5-MU. These results suggest that the capacity of alpha1-AR agonists (e.g. phenylpropanolamine) to suppress eating may be related to activation of the alpha(1A)-AR subtype, whereas cocaine does not act through the alpha(1A)-AR subtype to suppress eating nor does this subtype modulate cocaine-induced hyperlocomotion.